San Francisco 49ers star running back Christian McCaffrey departed Sunday night’s snow game against the Buffalo Bills early in the second quarter due to a knee injury.

The 49ers originally listed McCaffrey as questionable to return shortly after he left the playing surface for further examination. However, San Francisco coach Kyle Shanahan later told NBC that the 28-year-old was done for the game.

“He’s not going to return,” Shanahan said in an interview at the start of the third quarter.

McCaffrey had 53 yards on seven carries and caught two passes for 14 yards before exiting.

McCaffrey was playing in just his fourth game of the season after missing the first eight due to Achilles tendinitis in both legs.

He was averaging just under 10 yards per carry prior to the play on which he was hurt. McCaffrey caught a toss from quarterback Brock Purdy with under 11 1/2 minutes to go in the first half and quickly dropped to the ground for a 5-yard loss and then headed to the sideline.

McCaffrey was the NFL Offensive Player of the Year last season, when he led the league with 2,023 yards from scrimmage: a league-leading 1,459 rushing yards and 14 touchdowns plus 67 catches for 564 yards and seven scores.

McCaffrey hasn’t scored a touchdown in his four appearances this season. He has rushed for 202 yards on 50 carries and caught 15 passes for 146 yards.

Buffalo led 21-3 at halftime.