49ers vs Cardinals Week 3 Preview

The Arizona Cardinals and San Francisco 49ers will meet in Santa Clara on Sunday for Week 3 action, giving Jonathan Gannon's squad their first NFC West tilt of the 2025 season.

The Cardinals swept the season series between the two sides last year, though Kyle Shanahan and co. are hoping to write a new script despite the projected absence of starting quarterback Brock Purdy.

Injuries have riddled both sides in the early stages of the year - so it could be anybody's game when kickoff finally rolls around.

To help gain a better aspect from San Francisco, we paired with 49ers On SI's Jose Sanchez to answer a few questions:

Q: Who do you think plays on Sunday between Brock Purdy and Mac Jones? Will it even make a difference? 

Sanchez: Kyle Shanahan announced it's "highly unlikely" that Brock Purdy starts, which is the right call to sit him and start Mac Jones. There's no need to rush Purdy back as if they're a desperate team. As for a difference, there is because Purdy is better, especially from a mobility aspect.

But Jones does have better velocity on his throws and an arm, so that gives the 49ers a new wrinkle on offense. Jones does a fantastic job of shrinking the hole left by Purdy, and it will be proven again in this matchup.

Q: The 49ers are 2-0 - how have they looked so far? 

Sanchez: The 49ers have looked similar to what they were last year on offense. It's a little tough to project how good they will be since Purdy has only played one game, and he was only decent in his lone start. Either way, they can move the ball and play efficiently. The real eye-opener is with their defense. I never would've imagined they would look this solid through two games.

Yes, they have Robert Saleh back, who is a phenomenal coordinator, but they're playing with a handful of rookies, second-year players, and first-time starters. There were supposed to be early growing pains, but it looks like they're able to mitigate that so far. It's coming together nicely, especially with their run defense. It is vastly improved as they're ranked second-best in team run stuff rate (25 percent). It'll be exciting to see how they look against James Conner and Kyler Murray running.

Q: How does San Francisco view the Cardinals as an opponent in 2025? 

Sanchez: They're not fearful of Arizona (or any opponent), but they know they have to lock in and play at their best. It's always been a scrappy matchup with the Cardinals, no matter how good or bad either team is. I think that's significantly due to Kyler Murray. Throw away any stats of his when he plays the 49ers.

The reality is, he gives the 49ers headaches. It's funny how Matthew Stafford is the best quarterback in the division, but they play Stafford way better than they do Murray. Nick Bosa says they have a plan in place for Murray, which only took them six years, so we'll see if it works.

Q: Key matchup that will decide the game?

Sanchez: The key matchup will be limiting Murray. He's always the reason they're alive in games against the 49ers and why they have won games against them. His arm strength is a threat despite some accuracy issues; his mobility is annoying with his backyard plays and a threat to be a runner. Getting pressure on him will be tough, especially since he's one of the best this season at getting the ball out of his hands.

If the 49ers can make Arizona one-dimensional, it'll be easier to account for the several ways Murray can hurt them. Otherwise, Trey McBride will have a field day with Murray because the 49ers' safeties are inadequate.

Q: Game prediction?

Sanchez: I have the 49ers emerging as the victors. It'll be closely contested early on before the 49ers start to get momentum going with their in-game adjustments. I just think with the way the 49ers' defense is playing, it'll be enough to finally keep Murray in check and force him to turn it over. But that will only matter if Mac Jones doesn't turn it over either, because he's always good for one, it seems.

I see the score being 49ers 27, Cardinals 20.

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