Myers, 24, broke a bone in his leg, the Sabres said.
Myers had three goals and five assists in 39 games this season, with a minus-8 rating. He was in the first season of a seven-year, $38.5 million US contract.
The Sabres weren't specific in their statement as to when and how Myers got hurt in the game, though it may have come from a shot-blocking situation.
Buffalo was drubbed at home 5-1 by the Canadiens on Thursday and sit 11th in the Eastern Conference.
The former Calder Trophy winner Myers didn't give a hint of the injury when talking to the Buffalo News after the desultory defeat.
"It was the worst effort the Buffalo Sabres have put on the ice since I’ve been a part of it," he told the newspaper.
The Sabres host Philadelphia and Tampa Bay in games this weekend.