Jennifer Lee Chan of NBC Sports reported during the Bears game that Breida's ankle was "heavily taped" while he was still trying to return. Pettis sustained an MCL injury as well, according to Matt Maiocco of NBC Sports Bay Area.
Breida had 20 rushing yards on four carries before coming out of the game.
Signed by the 49ers as an undrafted free agent out of Georgia Southern in 2017, Breida has emerged as one of San Francisco's few bright spots in an otherwise disappointing season.
He was initially thrust into the starting role in training camp when Jerick McKinnon tore his ACL. He ran with his opportunity, sitting fourth in the NFL with 10 carries of at least 20 yards and ranking fourth with 5.3 yards per attempt.
However, the 49ers' season was thrown off course when quarterback Jimmy Garoppolo tore his ACL in Week 3 against the Kansas City Chiefs.
Breida has been one of the few steady forces for Shanahan, though he has been banged up at times. He sat out Week 14 against the Denver Broncos with an ankle injury.
San Francisco will turn to Jeff Wilson Jr. in the backfield to provide support for quarterback Nick Mullens.