It's unclear when Dareus hurt the hamstring. He watched the final portion of practice, including a red zone and goal line drill, from the sidelines and at one point spoke with trainers and coach Doug Marrone.
The Bills have an off day Thursday as they travel to Charlotte for their next preseason game Friday night against the Carolina Panthers. This injury puts Dareus' status for the preseason game in doubt.
In Dareus' place, journeyman defensive tackle Landon Cohen saw first-team reps with the defense. Marrone noted after practice that Cohen had two tackles for a loss in Sunday's preseason opener and deserved an opportunity for increased reps.
Meanwhile, safety Da'Norris Searcy remained out of practice Wednesday after leaving Tuesday's practice early for a personal situation.
"I missed him a couple times. I got in touch with him when we were on the field during the break [in practice]," Marrone said. "He has a family situation that he's excused from, obviously, and he's dealing with that.
"He wants to come back [for the game]. I told him just to make sure he has everything in order before he does."