Mack sustained a broken fibula in his side's win over the Pittsburgh Steelers, and requires surgery. The 28-year-old could return in eight weeks if he has only suffered the break in his leg.
Bryant tore his ACL in the victory at Cleveland Browns Stadium, and will require surgery that will rule him out for the rest of the season.
"It's tough," head coach Mike Pettine said on Mack's injury. "It's not just losing his play but it's also an emotional letdown as well. A guy who exemplified everything you're trying to get done."
The Browns are 3-2 in their season following their victory over the Steelers.