Chris Robshaw has been ruled out of England's autumn internationals after undergoing surgery.
Robshaw picked up a knee injury during Harlequins' Gallagher Premiership loss to Saracens and, having undergone surgery, he will be out for eight weeks.
The news comes a day after Saracens No 8 Billy Vunipola was ruled out of the four November Tests with a broken arm and is the latest injury setback to hit Eddie Jones' squad.
Harlequins head of rugby Paul Gustard said: "We are hugely disappointed to lose Chris for a short period of time, while he recovers from this injury.
"Not least because he has been one of our standout performers across our first seven games this season and also because this period in the calendar provides the opportunity to represent England in the autumn Internationals and I am sure he would have featured strongly in Eddie Jones' plans for those matches.
"Knowing Chris' character and resilience, I am confident he will make the most of this opportunity and come back even better and stronger.
"He will still play an active role in leading our team, despite not being able to take the field."
Robshaw and Vunipola add to mounting injury concerns for Jones, who will name his squad for the Quilter Internationals on Thursday.
Exeter Chiefs' Sam Simmonds is out for six months due to an anterior cruciate ligament injury while Joe Launchbury is unavailable after also undergoing knee surgery.
England will also be without winger Anthony Watson (Achilles), centre Jonathan Joseph (knee), prop Ellis Genge (knee), prop Beno Obano (knee), scrum-half Dan Robson (ankle), while centre Ben Te'o (calf) stands just an outside chance of playing any part.
Saracens prop Mako Vunipola and lock Nick Isiekwe suffered calf and ankle sprains respectively at the weekend and are also doubts to take part in the autumn schedule.
Nathan Hughes' availability is uncertain as he faces a disciplinary hearing on Wednesday for punching Gloucester's Lewis Ludlow.
England take on South Africa, New Zealand, Japan and Australia in November, with each game exclusively live on Sky Sports.