ORCHARD PARK — San Francisco running back Christian McCaffrey suffered a knee injury that coach Kyle Shanahan described as “potentially” season-ending in the 49ers’ 35-10 loss to the Buffalo Bills on Sunday night.

Shanahan said McCaffrey is believed to have injured his posterior cruciate ligament, which connects the thigh bone to the shin. He said he had no timetable for McCaffrey’s return but acknowledged the All-Pro’s season could be over.

“I think PCL is usually a couple weeks, but I’m not exactly sure yet,” Shanahan said.

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Latest Setback in Frustrating Season

It’s the latest setback in a frustrating season for the 2023 offensive player of the year, who missed the Niners’ first eight games with Achilles tendinitis and has not been his usual explosive self since returning. And it’s another blow for a team that has battled injuries all season, was missing five starters against Buffalo, and dropped its third straight.

San Francisco (5-7) sits alone in last in the NFC West standings, two wins behind division-leading Seattle, and in jeopardy of missing the playoffs a year after losing to Kansas City in the Super Bowl.

“He’s one of the best running backs in the league,” quarterback Brock Purdy said. “When you lose him like that, I think it takes away just sort of how we do some things in the offense.”

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McCaffrey’s Injury Details

McCaffrey stepped awkwardly on a sweep to the left on a snow-slicked field and went down almost immediately for a 5-yard loss. He went to the sideline and was examined in the medical tent before limping toward the locker room. The Niners announced before the start of the third quarter that he would not return.

Shanahan said he believes McCaffrey hurt his knee when he got tackled by Taylor Rapp at the end of an 18-yard run earlier in the drive.

“It looked like he just got shoe-stringed there, he was about to break a house call,” Shanahan said. “It was frustrating. He had a great week of practice. I could feel his urgency and stuff. Thought he came out great, looking real good.”

McCaffrey’s 19-yard run in the first quarter was his longest of the season, and he had seven carries for 53 yards and two catches for 14 yards before getting hurt.

“He was on fire man,” Purdy said. “He looked great, hitting the holes hard, bouncing off guys, and making some great plays.”

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49ers’ Struggles in Wintry Conditions

Very little went right for the 49ers in a game that was played in wintry conditions, with snow falling throughout the night.

Jake Moody missed two of three field-goal attempts. San Francisco lost three fumbles, including fullback Kyle Juszczyk getting the ball punched out of his arms at the Buffalo 1 to end San Francisco’s first drive of the second half.

Star linebacker Fred Warner, who continues playing with a broken bone in his ankle, also left the game with cramps, and was receiving intravenous fluids when James Cook scored on a 65-yard run to put the Bills up 14-3.

“Demoralizing,” said Warner, who returned to finish the game. “I felt like I let my team down by going in the locker room and then that happens.”

The 49ers had success rushing for 153 yards in snowy conditions. J.P. Mason had 73 yards on 13 carries, and Issac Guerendo ran for a 15-yard touchdown in the third quarter.

“Our goals was to run the heck out of the football, keep Josh Allen off the field,” tight end George Kittle said. “And I think we did a really good job of that. But we have to score points.”

Kittle had a 7-yard reception on the 49ers’ first play, but did not catch another pass in the game.

“It feels dark and gloomy and absolutely depressing,” Kittle said. “Football is tough man. Stuff happens and you’re either going to let it beat you down into oblivion and just give up, or you are going to continue to go out there and swing and fight every day that you have left.”