SANTA CLARA -- LaMichael James' knee injury is expected to sideline him for the start of the 49ers' season, which opens Sept. 8 against the Green Bay Packers.
James, a return specialist and reserve running back, sprained the medial collateral ligament in his left knee during Thursday night's exhibition finale at San Diego, the Sacramento Bee first reported Friday.
Consequently, the 49ers will have to adjust their return units, read-option offense and perhaps even their roster, which must be cut to 53 players by 3 p.m. Saturday. The 5-foot-9 James could be out a few weeks, but he's proved to be a quick healer in the past.
Punt-return duties likely will fall to Kyle Williams, who did not play in the exhibition season as a precaution. Williams has said he's recovered from a training-camp hamstring strain and last season's anterior-cruciate-ligament tear.
Perrish Cox, the 49ers' No. 5 cornerback, also gained experience this exhibition season returning punts and kickoffs. Roster hopefuls Chad Hall and Lavelle Hawkins could be in the mix, too, along with rookie wideout Quinton Patton.
Of James' 24 exhibition carries, seven saw him stopped for negative yards, and he averaged just 1.8 yards per carry over his final 20 rushes. The former Oregon standout had two carries for minus-4 yards and a 10-yard punt return Thursday before getting hurt.
Last season, James didn't debut as a rookie until December when he replaced an injured Kendall Hunter as the No. 2 running back and kickoff returner. After averaging 4.6 yards on 27 carries in the regular season, James improved in the postseason with a 5.9 average, and he scored his first career touchdown in the NFC Championship win at Atlanta.
In the 49ers' divisional playoff win over the Packers, James had three carries for 21 yards, a 7-yard reception and a 23-yard return of the opening kickoff.
Wallace, signed only a week ago, was trying to press his way into the conversation as a backup behind starter Colin Kaepernick. But Colt McCoy secured the No. 2 job, leaving Wallace to challenge rookie B.J. Daniels for a potential third-quarterback role.
Instead, Wallace surrendered and did not to travel to the team's final exhibition game. Yee told The Bee that Wallace met with Jim Harbaugh the morning of the game to inform the coach he didn't want to play if it meant mop-up duty at the end of the game.
Staff writer Daniel Brown contributed to this report.
Green Bay at 49ers, 1:25 p.m. FOX