England centre Manu Tuilagi has been ruled out for six months after tearing his Achilles in Sale's win over Northampton Saints on Tuesday.
Tuilagi will undergo surgery next week, and the injury will rule him out of England's autumn internationals as well as next year's Six Nations championship.
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"Manu will be a loss to England and Sale," Sale director of rugby Steve Diamond said. "He'll be out for six months. It's brutal what we're playing at the minute.
"Dan Biggar fell on him, so it was an accident. These things happen. I think it might have been a jinx, me saying before the game that we've got nine out of nine games out of him and boom, that happens. So I'll keep my trap shut in future.
"Rather selfishly, after this game and the play-offs we probably wouldn't have seen Manu until April with the England commitments and EPS rest periods."
Courtney Lawes is also a doubt for the start of England's international schedule due to an ankle injury that he sustained in the same game, leaving him on crutches.
Lawes departed in the ninth minute after falling awkwardly when challenging Tom Curry for a high ball, the Saints second row catching his right ankle in the turf as his body twisted on landing.
England head coach Eddie Jones is due on Monday to announce a preliminary squad for fixtures against the Barbarians and Italy that take place at the end of next month as the prelude to the Autumn Nations Cup.
Tuilagi and Lawes would be fully involved throughout the campaign and their absence would be a major setback to Jones as he targets the win in Rome on October 31 that might deliver the Six Nations title.
Tuilagi joined Sale on a one-year deal in the summer after being released by former side Leicester, the club he joined as a teenager.