The 49ers, already without starting left tackle Joe Staley, will not have right tackle Mike McGlinchey for the next four to six weeks.
49ers coach Kyle Shanahan announced Wednesday that McGlinchey will undergo arthroscopic surgery on his left knee.
Staley remains out after fracturing his fibula in Week Two.
The team also won’t have fullback Kyle Juszczyk for about a month after he sprained his MCL on Monday night.
The 49ers are expected to start Daniel Brunskill at right tackle in McGlinchey’s absence.
Brunskill played in the Alliance of American Football last spring, but he has never started an NFL regular-season game. He has eight offensive snaps this season in his only career action.