England prop Andrew Sheridan has been ruled out of the Rugby World Cup after injuring his left shoulder in the opening match against Argentina.
Sheridan has had two operations on the same shoulder and returned from right shoulder surgery for England's final World Cup warm-up against Ireland.
The Sale loose-head, 31, will return home for further treatment.
"It's sad for Sheri, he's been unlucky. We brought five props so have options," said England boss Martin Johnson.
England will decide on a replacement in due course but under World Cup rules Sheridan will not be allowed to rejoin the squad in New Zealand.
Matt Stevens and Alex Corbisiero will compete for Sheridan's starting spot, while Northampton prop Paul Doran-Jones and Wasps' Tim Payne are the most likely options to replace him in the party, having been included in England's initial 45-man training squad.
However, England do not have to replace like for like and may wait until after Sunday's match against Georgia to assess the fitness of flanker Lewis Moody.
Moody sent his commiserations to Sheridan via Twitter, saying "gutted for sheri, this sport of ours takes a serious toll on the body. get fit soon bud."
Sheridan, a member of the 2005 and 2009 British and Irish Lions squads, is considered one of the world's most powerful props and won his 40th Test cap in the 13-9 win over Argentina on Saturday.
But after damaging his left shoulder against the Pumas, scans sent back to specialists in the UK suggested the injury was significant enough to return home for further medical investigation, subject to the approval of the World Cup medical director.
Sheridan, who played in the 2007 World Cup final, was out for almost a year following two operations on a dislocated left shoulder in October 2009.
He won his 37th cap when England beat Wales in Cardiff at the start of the 2011 Six Nations, but missed the subsequent game against Italy because of back injury, and on his return against France, he strained a calf muscle and missed the final two Six Nations matches.
Following further surgery to his right shoulder, he was not selected for England's first two World Cup warm-up games against Wales, and is unsure whether he now needs another operation.
"I have to wait till I get back home and see the surgeon - I am quite well acquainted with him now," Sheridan said. "He will give me some good advice and see if I need an operation."
England are already missing lock Courtney Lawes for the next two matches against Georgia and Romania after he was banned for two weeks for using his knee on Argentina hooker Mario Ledesma.
But Johnson is optimistic Moody will be fit despite not having played since limping out of England's first World Cup warm-up with knee ligament damage.
"We are hopeful he is going to be good to go," said Johnson. "We talked last week that he wasn't far off being fit. Another week is always better when you've been injured for a long time but, at some point, you've got to go and we are hopeful."
Johnson is planning to rotate much of his squad for the Georgia game to expose most of his squad to World Cup action.
"We need to get the bulk of the squad on the field starting a game if we can because they need to be ready to play," said Johnson.
"You can't sit them out for a few weeks and then say 'this is the biggest game of your life on Saturday - how are you fixed?'
"We will make our decisions before the Scotland-Georgia game."