Derek Carr suffered a broken right fibula while getting sacked early in the fourth quarter Saturday and is out indefinitely.
Carr will undergo surgery on Sunday and the Oakland Raiders will start Matt McGloin at quarterback.
"It obviously is a blow," Jack Del Rio said. "That's what teams do; teams have to find a way to pick up and move on. We'll rally around the next guy as best we can. That's what you do.
"It will be incumbent on the offensive line and the backs to do more. The defense to do more. The special teams to do more. As a team, pick it up and do more to fill in. Obviously, it's a big setback."
In obvious pain, Carr appeared to mouth, "It's broken," as team medical personnel attended to him.
Carr, 25, could not put any weight on his right foot and had to be helped to the sideline.