"Unfortunately Kawika had a lot worse of a problem than we had anticipated," Bills coach Chan Gailey said. "It was going to be quite a few weeks, and we just couldn't wait."
Gailey added that it was too early to tell if Mitchell would need surgery to repair the problem.
A backup to Andra Davis, Mitchell was coming back from a right knee injury that forced him to miss the final 11 games last season after he went on IR.
The Bills signed free-agent linebacker Akin Ayodele to replace Mitchell.
Ayodele practiced with the team Friday, but will be inactive for Sunday's season-opener against Miami. He is entering his ninth season and joins the Bills after being released by Denver last month.
Ayodele started 15 games last year with the Dolphins.
Starting outside linebacker Reggie Torbor (chest) and backup linebacker Antonio Coleman (hamstring) are out for Sunday's game. Starting safety Jairus Byrd (groin) likely will play after practicing all week.
Byrd hasn't played in nearly a month after undergoing groin surgery. He earned a Pro Bowl selection as a rookie last year after finishing tied for the NFL lead with nine interceptions.