Christian McCaffrey’s season may be over.

The 49ers running back went down with a non-contact knee injury early in San Francisco’s 35-10 loss to the Buffalo Bills on Sunday night. Head coach Kyle Shanahan said after the game at Highmark Stadium that McCaffrey sustained a “potentially” season-ending PCL injury. Further specifics are not yet known.

McCaffrey, after taking a pitch to the right, suddenly pulled up and then gave himself up in the backfield without any contact. It looked as if McCaffrey pulled something in his leg, as he limped for a few steps before sliding down. He jogged off the field, and went into the blue medical tent on the sideline a few moments later.

McCaffrey walked to the locker room on his own power with a team athletic trainer minutes later. The 49ers initially said he was questionable to return with a knee injury before ruling him out to start the second half. He finished with 53 rushing yards on seven carries, and he had another 14 yards on two catches. He reportedly left the locker room after the game on crutches wearing a knee brace.

McCaffrey missed San Francisco’s first eight games of the season due to Achilles tendinitis and calf tightness. He flew to Germany to receive treatment from a specialist in September after landing on injured reserve. Sunday’s game was just his fourth of the season. He entered the night with 149 rushing yards, and he’s yet to score a touchdown this season.

McCaffrey’s injury is the latest that the 49ers are dealing with in recent weeks. They were without quarterback Brock Purdy last week in their loss to the Green Bay Packers due to a shoulder injury, though Purdy started on Sunday night. Both Nick Bosa and Trent Williams were out on Sunday night with injuries, too. Tight end George Kittle returned for a second straight game after missing time with a hamstring injury earlier this month.

The Bills rolled to a dominant win on Sunday night without McCaffrey on the field. Quarterback Josh Allen led Buffalo to the 25-point win, and he was credited with throwing and catching a touchdown pass on the same play in a wild showing in the second half. That pushed Buffalo to 10-2 on the season, which has it just a step behind the Kansas City Chiefs atop of the AFC race.

The 49ers have now lost three straight games and sit at 5-7 on the season. They are in last in the NFC West standings entering next week’s game against the Chicago Bears.