Week 3 Preview - 49ers vs Cardinals
The San Francisco 49ers (2-0) have their first divisional matchup of the season as they take on the Arizona Cardinals (1-1) at home. The game is at 4:05 PST.
Injury Report
Cardinals:
S Dadrion Taylor-Demerson is OUT with a back injury.
DT Roy Lopez is listed as questionable with a groin issue. He did not practice on Wed/Thurs, and was limited on Friday.
CB Max Melton is listed as questionable with a toe issue. He did not practice on Wednesday, and was limited on Thurs/Fri.
No other Cardinals have a game designation and are all expected to play.
49ers:
DE Nick Bosa is OUT with a calf injury.
EDGE Romello Height is OUT with a hand injury.
DT James Thompson Jr is OUT with an ankle injury.
WR Demarcus Robinson is OUT with an ankle injury.
WR Mike Evans is listed as questionable with a hip issue. He did not practice on Wed/Thurs, and was limited on Friday.
No other 49ers have a game designation and are all expected to play.
Matchups to Watch:
Cardinals Run Defense
Through two weeks, the Arizona Cardinals run defense has been elite! The defensive front was perhaps underrated by the media.
An interior trio of Walter Nolen, Roy Lopez, and Dante Stills is nasty against the run. Nolen is an absolute freak, and Roy Lopez is one of the best nose tackles in the NFL. And Dante Stills has the size and power to be very effective against the run. He and Nolen are athletic enough to slant and blow up rushing lanes.
And having Josh Sweat, Zaven Collins, and Baron Browning on the edge is a nice touch to complete this defensive front.
In the first two weeks, opponents have run for just 3.06 yards per carry up the middle on 32 carries against Arizona.
For San Francisco, their Week 2 run game was reminiscent of 2025. Meaning it was bad. Watching the Seahawks run game in Week 2 was nice for myself, and probably the 49ers, as Brian Fleury is Seattle's playcaller. Fleury spent the last 6 seasons as an offensive assistant with San Francisco, so the run concepts match what the 49ers do fairly closely.
Here is a two tweet thread showing some of what could work for San Francisco against the Cardinals. Arizona is good at blowing up running lanes, but the 49ers have these cutback lanes "baked in" to their outside zone concepts. Christian McCaffrey had a couple nice runs when he hit these cutback lanes in Week 1. He'll likely have to do so again to overcome the way Arizona crashes the rushing lanes.
The two problems that are easy to envision for the 49ers against the Cardinals starts with the defensive front. I mentioned Nolen and Stills' ability to blow up gaps when slanting. Seattle's tackles struggled with this, simply because Nolen and Stills are physical freaks who are already in an advantaged position. With these two often slanting in from the 4i technique, it's really difficult for offensive tackles to reach and cut them off, especially on inside runs. Whenever the OT has that assignment, Nolen and Stills just get upfield too quickly to be handled properly.
An issue I saw with the 49ers run game in Week 2 was having a defender seemingly unaccounted for in the box. Oftentimes it appeared that this was simply due to a skill position player having to come a long way to make the block, and the difficulty of their blocking assignment halted the success of the run design. But, as I do not have the run designs in hand, it's possible this was an offensive line issue. Were they just failing to climb to the second level?
Regardless of who was responsible, it will remain a difficult task against Arizona. Linebacker Mack Wilson(#1) is very good at getting downhill. He takes effective routes and is quite slippery. They also bring their safeties down, Budda Baker and Andrew Wingard, both of whom are capable of making tackles in the box.
While I discussed the 49ers run game just as much as Arizona's run defense, I wanted to emphasize the Cardinals run defense more simply because they have been susceptible to being attacked over the middle of the field.
A third of passing attempts against the Cardinals have been 10+ yards over the middle of the field, with a lot of those being in-breaking routes. I do not think their linebackers are particularly susceptible to play-action, but Arizona has been attacked there regardless.
If the Cardinals run defense continues to show up and can stifle the 49ers questionable running game, it will force San Francisco into obvious passing situations. This will naturally make the passing attack easier to defend, because the middle of the field should not be quite as accessible.
49ers Middle of the Field Pass Game
The 49ers offense under Kyle Shanahan has classically attacked the middle of the field, often with in-breaking routes that are opened up by play-action. Some of their top pass catches have dominated in the middle of the field for various reason.
Brandon Aiyuk was an elite separator who was always available to target, and was good after the catch. Deebo Samuel would get targets when the middle was vacated thanks the play-action, and take it to the house. And Jauan Jennings, an underrated route salesman and after the catch player, had the frame to catch any ball thrown in between the safeties and linebackers.
Through two weeks of the 2026 season, this has not been the case. The 49ers have really only hit one true deep dig route, one to Deebo Samuel against Miami. There were a couple balls over the middle to George Kittle as well, but not what I picture when I say "Kyle Shanahan over the middle of the field."
This raises a few questions:
Will we see the classic 49ers offense at some point this season? Or is the personnel just too different? Mike Evans is a great weapon all over the field for many reasons, but he's not the typical dig route connoisseur.
Again, if the Cardinals are able to shut down the 49ers run game, they will not be as exposed to middle of the field attempts. I don't think the Cardinals linebackers are too bad in coverage, mostly meaning that they do get to the proper depth in their zone drops. Arizona's backers aren't that bad against play-action pass, but they do commit to the run.
The two offensive playcallers the Cardinals have seen both come from Kyle Shanahan, in Mike McDaniel and Brian Fleury. So we did see both offensive coordinators move Arizona's backers, even without play-action, usually by widening them out with motion to create a slightly larger throwing window over the middle.
CB Max Melton has been banged up and is officially listed as questionable, while it appears CB Garrett Williams will make his season debut after tearing his achilles in Week 16 of 2025. So it is likely Arizona will roll out their starting secondary. We'll see if that changes the gameplan at all, and how comfortable Williams is guarding Mike Evans on the perimeter.
Will the 49ers intermediate passing game return against the Cardinals, or do they keep pushing it to the sidelines with Mike Evans, and maybe even with the speedy Jacob Cowing, who may be the one asked to step up with injuries.
Interior Battle in Trenches
The 49ers interior defensive line has already been weak, and the line as a whole just got weaker. CJ West has been playing nose, and he's been placed on IR. DT James Thompson Jr and DE Nick Bosa will both miss this week, and likely more time, and EDGE Romello Height will also be out this week, making this San Francisco front particularly thin.
Initially, I was pondering whether or not the 49ers interior could look better without CJ West, as NT Naquan Jones was signed off of Minnesota's practice squad to replace him. Jones is a veteran who fits more of the traditional nose tackle mold, holding double teams and being more stout than explosive against the run. But with Bosa out, even though he rarely lines up on the interior, it's hard to imagine the 49ers front improves.
The Cardinals interior offensive line has struggled a bit early in the season. The Chargers only recorded one interior pressure in Week 1, but consistently blew up run plays in the A gap. And Seattle's interior group combined for 6 pressures and 2.0 sacks in Week 2, although their unit will do that to anybody.
The thing the Chargers and Seahawks have in common is a physical nose tackle. Will Naquan Jones be enough to disrupt Arizona's run game? That is a question I have no idea how to answer.
The Cardinals have not yet had success running up the middle. Outside the tackles, they've had 10 rushes for 63 yards, compared to 36 rushes for just 109 yards(3.03 ypc) in between the B and A gaps. Does this have a chance to change against San Francisco's weak interior defensive line?
A somewhat notable part of the Cardinals run game is insert blockers.
It makes sense that head coach Mike LaFleur likes to use them, as it's kind of a staple of Sean McVay's offense with Puka Nacua and Jordan Whittington. LaFleur coached under McVay for the last three seasons.
A wide receiver will insert into the C gap to either chip the end or climb to the backer, acting as a fullback. While this is a staple of the running game, it's also meant to help set up play-action. Linebackers will fall for the fake when they see the receiver insert into the gap, and the receiver, who the LB (or slot defender) is often responsible for, just runs by them.
The issue is the Cardinals use Kendrick Bourne in this role. And despite how much I love the 10 year NFL vet and former 49er, Bourne is not built for that role. Meaning it does not add much to the run game for Arizona.
Honestly, if Arizona elects to use Bourne this way frequently against San Francisco, I see this as an advantage for the 49ers. I'd prefer to see Bourne try to take Fred Warner, Dre Greenlaw, Jaden Dugger, or even Upton Stout, out of the play, rather than having the 49ers interior defensive line be left on their own, allowing the Cardinals offensive line to climb to the second level.
I wrote these "Matchups to Watch" before it was reported Nick Bosa went down. Honestly, with his injury, maybe this should this be about the 49ers ability to contain the Cardinals outside zone runs. It is definitely something else to note down.
If the 49ers can't contain the outside runs, they'll be able to stretch the 49ers defensive front wider, perhaps opening up the interior rushing attack. In the end, it's really up to members of the 49ers defensive line to step up their play against the run. Especially with how the linebackers and safeties have been playing the run, they are all doing their part.
Prediction:
49ers 28, Cardinals 23
The Cardinals will have the opportunity to showcase the ceiling of their offense on Sunday. San Francisco is trotting out a backup defensive line that already struggled to stop the run. While their back seven has been strong, that could change if the front can't get any pressure.
Raheem Morris has yet to unleash his typical blitz heavy defense, and I expect that to change on Sunday. The 49ers should see closer to a 33% blitz rate, rather than the 15% we've seen through 2 weeks. And about half of the blitzes that we have seen from San Francisco come from a 5-man front, where all five just rush. Morris hasn't exactly been deep in his bag of tricks. He may have to be with the state of the 49ers defensive line.
I do not expect the 49ers to dominate on offense like they did in Week 2, but I do expect long drives to end up being touchdowns. The ground game may struggle, but if the offense is marching down the field, I don't see Arizona slowing it down enough to force a field goal.
Arizona's ground game should be efficient enough to sustain drives and collect points, even if they are stuffed in the redzone.
I trust both quarterbacks to not turn the ball over in this Week 3 matchup. While Purdy will have a lot on his plate, he's just been so elite to start the season, I believe his groove will continue into Week 3. And Jacoby Brissett and the Cardinals offense should be able to move the ball without forcing any tough throws, so I anticipate Brissett having a clean game.
That does it for our 49ers Week 3 preview!
Let me know your thoughts on this Week 3 matchup, which matchups you think will have the biggest impact on Sunday, and your Week 3 predictions!
I have posted my full Week 3 predictions for the entire NFL slate on my Twitter/X, @GridironGoldM_.
Stay tuned for more NFL and 49ers articles, news, and opinions!
Comments