England second row Joe Launchbury will miss the November international series after undergoing surgery for a knee injury.
The Wasps lock, who has not played since mid-September, was expected to return to face Leinster in the Champions Cup this weekend.
But Wasps have announced he will be out 10-12 weeks, meaning he will likely not return before next year.
Launchbury -- who has earned 54 caps at international level -- is the latest casualty in a long list for Eddie Jones ahead of the matches against South Africa, New Zealand, Japan and Australia next month.
His Wasps teammate Dan Robson has also been ruled out after he suffered an ankle injury in Saturday's 35-21 defeat to Gloucester.
Robson was part of England's summer touring party to South Africa but has also undergone an operation which will see him miss around three months.
Meanwhile No. 8 Nathan Hughes is facing a ban for punching Gloucester's Lewis Ludlow in the head.
An RFU disciplinary panel will reconvene next week to decide his fate after they postponed a decision on how to punish Hughes.
A tweet the Wasps player sent out describing his first hearing on Wednesday as a "joke" may land him in further trouble.
Wing Marland Yarde was ruled out for the rest of the season earlier this week after dislocating his kneecap, while Johnny May's participation was put in doubt after he suffered a shoulder injury.
Jones announces his squad for the Autumn internationals on Oct. 18 before his players head to Portugal for a training camp.
They take on South Africa on Nov. 3, then New Zealand on Nov. 10, Japan on Nov. 17 and Australia on Nov. 24.