Alex Mitchell is set to miss England's opening November international against Australia on Sunday in the latest blow to the plans of coach Steve Borthwick.
Mitchell suffered a hamstring injury while playing for Northampton in the English Prem champions' 28-14 win over Gloucester on Saturday.
The scrum-half was left out of a 36-man squad announced by Borthwick on Monday.
Mitchell's Northampton teammate Archie McParland missed the Gloucester match because of a calf issue sustained during England's training camp last week.
McParland will also be sidelined when Australia visit Twickenham, but it is hoped the scrumhalf can recover in time to face Japan or New Zealand in the Nations Championship later in the month ahead of finals weekend.
Fin Smith, England's first-choice flyhalf and a Saints teammate of the injured scrumhalves, is in a race against time to face Australia following a calf strain.
Borthwick has called up Ben Spencer and Harry Randall to fill the gaps in his squad.
Senior Men Squad announcement 📢 Head coach Steve Borthwick has named his 36-player squad for the upcoming Nations Championship fixtures against Australia, Japan and New Zealand. @O2 | #WearTheRose https://t.co/Y5TDmPIgwP
— England Rugby (@EnglandRugby) November 2, 2026
England, who finished a lowly fifth in the 2026 Six Nations, have lost five of their past seven tests.
But despite that poor run, the Rugby Football Union announced in September that Borthwick's contract had been extended beyond the 2028 Six Nations – long after the end of next year's World Cup in Australia.
"These fixtures take on added significance this autumn as they represent our final opportunity to face southern hemisphere opposition before next year's World Cup," Borthwick said.
"Facing Australia next Sunday is an exciting challenge. They have played a significant amount of test rugby in recent months and we know the quality and experience they will bring."
England squad
Backs: Seb Atkinson, Fraser Dingwall, Immanuel Feyi-Waboso, George Ford, Tommy Freeman, George Furbank, Will Joseph, Joe Marchant, Cadan Murley, Harry Randall, Henry Slade, Fin Smith, Marcus Smith, Ben Spencer, Freddie Steward, Jack van Poortvliet
Forwards: Fin Baxter, Ollie Chessum, Arthur Clark, Alex Coles, Luke Cowan-Dickie, Ben Curry, Tom Curry, Theo Dan, Ben Earl, Greg Fisilau, Jamie George, Ellis Genge, Joe Heyes, Maro Itoje, Emmanuel Iyogun, George Martin, Asher Opoku-Fordjour, Tom Pearson, Henry Pollock, Will Stuart
Coach: Steve Borthwick (ENG)