The 2-0 San Francisco 49ers are poised to already do something in Week 3 that they failed to do last season: win two games within the NFC West.
Having already defeated the Seattle Seahawks in Week 1, a victory this Sunday over another division rival, the 2-0 Arizona Cardinals, would double head coach Kyle Shanahan’s squad’s NFC West win total from 2024’s abysmal 6-11 campaign.
And the prospects for achieving this in the Niners’ home opener are already lining up.
San Francisco has been no stranger to injury problems this season, highlighted by All-Pro tight end George Kittle (hamstring) landing on injured reserve after Week 1, while quarterback Brock Purdy (toe) missed Week 2’s win over the New Orleans Saints, giving way to a solid outing by his backup, Mac Jones.
While Purdy has a remote chance of playing on Sunday, one might make the argument the Cardinals are dealing with more urgent injury concerns that could open the floodgates to a possible 49ers offensive explosion.
Cardinals defense will be shorthanded in Week 3 vs. 49ers
Arizona is placing cornerback Garrett Williams and defensive lineman L.J. Collier on injured reserve, as head coach Jonathan Gannon told reporters ahead of the Week 3 NFC West showdown.
But the red birds’ injury woes don’t end there.
The Cardinals’ Week 3 injury report is concerning, and their secondary has been hit particularly hard with cornerback Sean Murphy-Bunting still on the non-football-injury (NFI) list and cornerback Max Melton limited with a knee injury.
Cardinals CB Garrett Williams and DL L.J. Collier are going on IR with a chance to return, Jonathan Gannon said.
CB Max Melton will be back at practice today.
CB Will Johnson will not be practicing this week.
Their status for Sunday in SF is still unknown.
— Josh Weinfuss (@joshweinfuss) September 17, 2025
Most provocative is the status of rookie corner Will Johnson (groin), who was one of Week 1’s best performers but whose injuries at Michigan ultimately forced him to fall into Round 2 of last April’s NFL Draft.
Gannon’s defense, including against the pass, has been stingy enough, allowing only 4.9 yards per pass attempt over the first two weeks, boosting another impressive stat of just 4.6 yards allowed per play, tied for fifth best. But it’s important to acknowledge Arizona’s first two opponents aren’t exactly projected to be heavy hitters, the Saints and Carolina Panthers, meaning those defensive numbers have to be taken into context.
Potentially missing Johnson and/or Melton, the Cardinals’ first serious threat might potentially be set up for a massive offensive showing regardless of who starts under center between Purdy and Jones.
And the Niners would love nothing more than to take advantage of Arizona’s injury woes by putting up some big numbers when the two teams square off on Sunday, Sept. 21 from Levi’s Stadium.
