The Arizona Cardinals left San Francisco on Sunday with more than just a tough one-point loss. They also lost one of their most important players and one of the most respected voices in their locker room.
James Conner Out for Season After Grueling Injury Versus San Francisco
James Conner’s 2025 season came to a crushing end when the veteran running back went down with a right foot injury in the third quarter against the 49ers.
After a low hit caused his leg to bend awkwardly, Conner stayed on the turf before being carted off the field. Tests confirmed the worst: he’ll need surgery and won’t play again until 2026.
For Cardinals fans, it’s a gut punch. Conner isn’t just a name on the stat sheet; he’s been the team’s workhorse and emotional leader since arriving in 2021. He delivered back-to-back 1,000-yard seasons, kept the chains moving in critical moments, and gave Arizona’s offense its edge. In many ways, he’s been the heartbeat of the team.
Head coach Jonathan Gannon couldn’t hide how much this one hurts.
“One of your leaders, a captain. You hate that it happened,” Gannon said. “I feel terrible, but I know he’ll take the right attitude and bounce back. Picking up that slack, both the player and the person, we’re all going to have to collectively do it.”
Now, the Cardinals will turn to second-year running back Trey Benson. He’s shown flashes of promise, but this will be his first real test as the lead back. Teammates and coaches alike will have to rally together to fill the massive void Conner leaves behind.
Trey Benson Set to Take Over, Short Week as Arizona Prepares for TNF
The timing of the injury stings even more because of how close Sunday’s game was. Arizona fell 15–16 to San Francisco, and it’s hard not to imagine what might have happened if Conner had been there to close out drives.
Even though Trey Benson’s value has risen since James Conner’s injury, I do see Benson performing at a borderline RB1 level the rest of the season. A big buy for me in both redraft and dynasty. I would try to buy in now before he gets a true RB1 workload.
— Sir Green Bean (@GreenFantasy247) September 24, 2025
Instead, the team now faces a short turnaround with Thursday Night Football against the Seattle Seahawks, a divisional matchup that suddenly feels even more daunting.
For Conner, it’s the start of another long road back. He’s no stranger to adversity, from his inspiring recovery from cancer during his college career at the University of Pittsburgh to his reputation as one of the NFL’s toughest players. While the rehab process will keep him sidelined this season, there’s no doubt he’ll attack it with the same determination he’s always shown.
Arizona will miss his presence every snap of 2025, but fans and teammates know this isn’t the end of Conner’s story. If history has taught us anything, it’s that he’ll be back stronger, ready to remind everyone why he’s been the heart and soul of the Cardinals’ offense.

