49ers vs Cardinals: Key Injuries, Big Questions Shape Week 11 Showdown

Get a full 49ers vs. Cardinals Week 11 preview, including Brock Purdy’s return, key injuries, major matchups, and the factors that could decide Sunday’s game.

September 21, 2025; Santa Clara, California, USA; San Francisco 49ers running back Christian McCaffrey (23) during the fourth quarter against the Arizona Cardinals at Levi's Stadium. Mandatory Credit: Kyle Terada-Imagn Images | Kyle Terada-Imagn Images

The Arizona Cardinals play host to the San Francisco 49ers in Week 11 action, and there are several storylines to follow on both sides.

In Arizona, a mountain of injuries provides yet another hurdle for the Cardinals while the 49ers are getting Brock Purdy back as their starting quarterback.

To gain a preview of Sunday from San Francisco's side, we spoke with 49ers On SI's Jose Sanchez:

1. What's changed since the last time the Cardinals met the 49ers?

Jose Sanchez: A plethora of key players are out for the season due to significant injuries. The top difference is that their pass rush is nonexistent. They’re relying on players who they just signed or traded for a few weeks ago to help them. They’ve been blitzing at a higher rate too, but to no avail. Jacoby Brissett will have ample time to find receivers throughout the game.

2. How different do you think the offense will be with Brock Purdy?

Sanchez: Not significantly different. He adds off-schedule playmaking ability and probably more boot plays, but I wonder how much of that will be prevalent. He’s not 100 percent. Kyle Shanahan said the other week that he won’t be this season, so his turf toe is lingering mildly. Mac Jones was playing extremely well this season, so I’m curious what the difference will be.

3. What needs to happen for the 49ers to lose this game?

Sanchez: Brock Purdy will need to turn it over, which he’s prone to do. The 49ers cannot afford turnovers will their turnstile defense. With no pass rush and no more than a decent secondary, the defense is going to allow points. It’s on the offense to protect them with long sustained drives that lead to points with no turnovers. That will only increase the difficulty for their defense and force the offense to chase the game.

4. Whats one matchup you think can dictate Sundays outcome?

Sanchez: The Cardinals’ pass rush against the 49ers’ offensive line. They were disruptive last time, generating around 38 percent pressure. The 49ers’ offensive line struggles with physical defensive fronts. Purdy being mobile should help, but again, how mobile will he be with his turf toe still at play. Plus, Purdy is prone to holding the ball for too long, which will give the Cardinals’ pass rush plenty of chances to take over.

5. Whats your prediction?

Sanchez: I fully expect the 49ers to win this game but their will be ugly moments. Purdy will likely be rusty, and the 49ers’ defense will probably take a few drives before they tighten up. So long as the turnovers are nonexistent, this should be a smooth win for the 49ers after some early struggles. Let’s say a score of 49ers 23, Cardinals 17.