Named starting quarterback for the season, the third overall draft pick from the 2021 NFL draft completed 13 of 28 passes for 164 yards and an interception in the 49ers' Week 1 defeat against the Chicago Bears in poor weather.
The 49ers had high hopes for the 22-year-old, with Sunday's hosting of the Seahawks representing his first game at Levi's Stadium as a starter in the regular season.
His game lasted less than two drives, however, suffering an ankle injury after a rushing attempt and being replaced on the field by Jimmy Garoppolo.
The 49ers swiftly confirmed that Lance would be out for the remainder of the game, though concerns will be that he could be absent for an extended period.
Tight end George Kittle was already a significant absentee for Kyle Shanahan's side, though he returned to practice on Friday.