SANTA CLARA, Calif. — Arizona Cardinals running back James Conner suffered a season-ending right ankle injury during Sunday’s loss to the San Francisco 49ers, a source told ESPN’s Adam Schefter.

Conner was carted off the field after a 1-yard run with 12:26 remaining in the third quarter of the Niners’ 16-15 victory. The injury is considered “severe” and will require surgery, the source told ESPN on Sunday night.

After the game, Arizona coach Jonathan Gannon said he didn’t know the severity of the injury, as a prognosis hadn’t yet been made.

The Cardinals are heading into a short week before hosting the Seattle Seahawks on Thursday night.

Players from both teams took a knee as athletic trainers quickly attended to Conner after he went down. Players on the Cardinals bench walked onto the field to check on their captain as he was loaded onto the cart.

“It’s one of my best friends on the team,” backup running back Trey Benson said. “It was like a big brother to me — my mentor. He taught me a lot of stuff here, so it was tough [to watch].”

Quarterback Kyler Murray was visibly upset on the field while Conner was being examined.

“Yeah, it’s unfortunate,” Murray said after the game. “Just not only is he my teammate, I feel like that’s a brother of mine. Just to see him go down like that, you never want to see that. I understand it’s part of the game, but it is not ideal. All the work that he puts in and just who he is as a person, you don’t want to see him get hurt like that. Yeah, it’s tough.

“He’s everything, means everything.”

Gannon said injuries are part of the game and that players need to “just be trained” to get through it.

Conner, 30, had nine carries for 22 yards before his injury. He was coming off back-to-back 1,000-yard seasons — the first time he accomplished that in his career.

Conner signed a two-year extension in November 2024 that runs through the 2026 campaign. His $3.64 million base salary for this year is guaranteed for injury.

With Conner out for the rest of the season, Benson is expected to move into the starting running back role, followed by Emari Demercado and Bam Knight. Arizona also has Michael Carter, who had 131 yards and a touchdown on 35 carries last season, on the practice squad.

Arizona has carried four running backs this season, with three available on game day.