The team is awaiting further evaluation before determining whether McCoy can play Sunday against the Dolphins.
"He was tight in the hamstring, so we'll see what happens with our medical evaluation and all that," Bills coach Rex Ryan said after practice. "I'm not going to look into [his availability Sunday], but we'll see how he comes back."
Quarterback Tyrod Taylor said he did not recall when McCoy's injury occurred but said he noticed the running back's reps seemed limited during practice.
McCoy ranks second in the NFL this season with 587 rushing yards. He has averaged 6.4 yards per carry over the Bills' current four-game winning streak, amassing 470 rushing yards during that span.
If McCoy cannot play Sunday, backup Mike Gillislee would be expected to take most of the carries.
"We feel good about the guys that we do have, but that's assuming he won't play," Ryan said. "We'll see how it goes."
A solemn Rex Ryan addresses McCoy's injury
Bills coach Rex Ryan addresses LeSean McCoy's injury at practice and says it has nothing to do with Sunday's game.