The San Francisco 49ers placed running back Raheem Mostert on injured reserve Saturday due to a sprained left ankle.
Mostert must miss at least three games before he's eligible to return.
The postseason hero from last season missed two games earlier this season with a different ankle injury.
Mostert has rushed for 303 yards and one touchdown on 51 carries and also has 11 receptions for 150 yards and one score this season.
Mostert etched his name into team lore in January when he rushed for a franchise-record 220 yards and scored four touchdowns as the 49ers pummeled the Green Bay Packers 37-20 in the NFC Championship Game.
Jerick McKinnon (211 rushing yards, four total touchdowns) will be the team's lead running back for Sunday's game against the New England Patriots.
San Francisco also activated safeties Johnathan Cyprien and Jared Mayden from the practice squad. Receiver Jauan Jennings was placed on the practice squad injured reserve list.
The 49ers activated Cyprien and Mayden because starting safeties Jaquiski Tartt (groin) and Jimmie Ward (quadriceps) will miss Sunday's game.
--Field Level Media