Edwards missed his third straight practice Friday since knocking knees in a collision with running back Marshawn Lynch on Tuesday night.
"It's making minimal progress," Edwards said.
Edwards, who walked with a limp throughout the workout, was optimistic that he'll be ready for Buffalo's final preseason game against Detroit on Thursday.
The Bills host Seattle in their season opener Sept. 7.
Backup J.P. Losman will get the start against the Colts in place of Edwards.
Receivers Roscoe Parrish (knee) and rookie James Hardy (hamstring) also will not play against the Colts.