"Obviously that's a devastating loss to us and to him," coach Rex Ryan said Sunday.
Wynn is a key reserve for the Bills behind starting defensive ends Mario Williams and Jerry Hughes. If Wynn is out for the season, defensive end IK Enemkpali -- whom the Bills claimed off waivers last week from the New York Jets -- could have a stronger chance to make the 53-man roster.
Wynn had missed practice time earlier in training camp with a knee injury. He was on the field for 20 snaps Friday before the Bills announced him as being out for the game in the third quarter.
He played in 11 games last season for the Bills, recording 17 tackles and two sacks.