England flanker Chandler Cunningham-South faces two months on the sidelines after suffering an ankle injury in a tackle by international teammate George Ford.
The Harlequins star will need surgery after being hurt during his side's 28-24 defeat to Sale Sharks on October 11.
Cunningham-South was caught in a hip-drop tackle by Ford as he made a break late in the match.
The incident sparked confusion after referee Christophe Ridley initially awarded a penalty.
However, the decision was reversed because World Rugby's new ban on hip-drop tackles does not come into force until November 1.
The injury is a major blow for Cunningham-South, who will now miss England's November Nations Championship campaign.
Harlequins boss confirms surgery
Harlequins head coach Jason Gilmore has confirmed the 23-year-old faces a lengthy spell out.
Speaking about the incident, Gilmore said: "It's probably a frustrating one; on the linebreak against Sale, he copped a hip-drop tackle from behind."
He added: "He's going in for surgery, and he'll be out for two months."
Gilmore hopes to have Cunningham-South back for the next block of PREM Rugby fixtures, potentially against Leicester Tigers.
England suffer another injury setback
The news leaves England boss Steve Borthwick with another injury concern ahead of November.
Cunningham-South was already missing from England's latest training squad.
Borthwick's side face Australia on November 8, Japan on November 14 and New Zealand on November 21.
The flanker now looks set to miss all three matches, along with the Nations Championship finals.
His absence comes after England confirmed two players would miss their latest training camp.
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Three Harlequins players handed opportunity
Cunningham-South's absence also creates opportunities at club level.
Zach Carr, Lucas Schmid and Seb Driscoll could all benefit from more game time in the coming weeks.
Schmid has already impressed at number eight, while Driscoll has earned opportunities in the back row.
Gilmore will hope the trio can help fill the gap left by one of his most powerful forwards.
For Cunningham-South, the focus now turns to surgery and recovery ahead of a possible return in December.
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