England lock Courtney Lawes will miss the six-game autumn schedule after being sidelined for three months by an ankle injury.
The Northampton forward, who has won 85 Test caps for the national side, was injured during Saints' Premiership game against Sale Sharks last week.
In a statement, Northampton said: "Northampton Saints can confirm that, following consultation between the club's medical staff and a specialist, Courtney Lawes will undergo surgery on the ankle injury he sustained against Sale Sharks last week.
"The 31-year-old England lock will require a rehabilitation period of approximately 12 weeks."
It is a second major injury blow for England head coach Eddie Jones, with Sale centre Manu Tuilagi facing six months out after he suffered an Achilles injury in the same game on September 29.
Both players started last year's World Cup final against South Africa and they remain integral parts of Jones's plans.
England play the Barbarians in a non-cap international on October 25, followed by their delayed 2020 Six Nations clash against Italy in Rome six days later.
Jones's men then face Autumn Nations Cup matches against Georgia, Ireland and Wales, plus a Nations Cup play-off fixture in early December.
The Barbarians have confirmed that Chris Robshaw will play one final time in England before he starts a new club career in the United States with San Diego Legion.
"It is a massive honour and privilege to be able to wear the famous black and white shirt of the Barbarians and I will do so with great pride," said the former England captain.
"It has been a strange season and while I have not been able to play out my Harlequins career in front of fans, I am so happy I will have a chance to say farewell to England at Twickenham."