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Arizona Cardinals Announce Troubling News After James Conner Was Carted Off Against 49ers

Originally posted on Athlon Sports | By Paolo Songco | Last updated Sep 21, 2025 6:39 PM ET

The Arizona Cardinals aim to maintain their perfect record on Sunday as they face the San Francisco 49ers in a road game at Levi’s Stadium. The Niners, however, are also undefeated in two games played to start the season, which only means that one of these two sides will be going home with their first defeat.

Unfortunately for the Cardinals, they suffered a brutal blow in the third quarter after two-time Pro Bowl running back James Conner suffered what appears to be a significant ankle injury.

Conner took a hit as he ran for a one-yard gain up the middle. His right ankle was twisted and got caught underneath a Niners defender as Conner got tackled.

Slightly better view of the James Conner injury. In addition to MCL concern also concerned about an ankle fracture with this mechanism. Hope for the best but we’ll see #cardinals pic.twitter.com/lyQyv48G9S
— Tom Christ, PT, DPT, OCS, FAAOMPT (@FantasyInjuryT) September 21, 2025

Conner was seen grabbing onto his ankle as he lay on the field, and it looked like he was in significant pain. The injury was serious enough for the Cardinals to cart him off the field. The entire bench came to Conner's side to show their support, which emphasized the magnitude of the situation.

Prayers up for James Conner pic.twitter.com/KAdzPExqZ5
— FOX Sports: NFL (@NFLonFOX) September 21, 2025

It did not take long for the Cardinals to announce that Conner has been ruled out for the remainder of the game. The team has not revealed the extent of the injury, but they have labeled it as an ankle issue.

James Conner (ankle) has been ruled out.
— Arizona Cardinals (@AZCardinals) September 21, 2025

Conner will now undergo tests to determine how bad the ankle problem is. However, taking all things into consideration, it would not be surprising if this costs him multiple weeks on the sidelines. There is even some fear that this could have been a season-ending injury for the former Pittsburgh University star.

For now, however, the Arizona faithful will have no other choice but to hope and pray that Conner's injury is not as bad as it looks.

As of writing, the game is tied at 6-6 at the start of the fourth quarter.

This article first appeared on Athlon Sports and was syndicated with permission.

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