England captain Rio Ferdinand will miss the World Cup after a knee ligament injury suffered in training ruled him out for four to six weeks, the FA confirmed.
The injury-prone 31-year-old central defender went into a tackle with Emile Heskey and fell badly in the final minutes of their first training session in South Africa.
Tottenham's Michael Dawson will fly to South Africa as a replacement for the Manchester United defender, while vice captain Steven Gerrard will lead the team in their first match against the US on June 12.
"Further to a scan arranged by the England medical staff immediately after training on Friday afternoon, Rio has been ruled out for four to six weeks and will therefore unfortunately miss the World Cup," the FA said in a statement.
"Tottenham Hotspur's Michael Dawson has been contacted today and will fly to South Africa on Friday evening.
"Steven Gerrard will lead the England team as captain in the tournament."
England Manager Fabio Capello said: "It is obviously bad news and everyone with the squad is very disappointed and sorry for Rio.
"It was an accidental injury in training, but had nothing to do with the pitch."
The Italian also confirmed that goalkeeper David James had missed training due to a nagging knee injury aggravated by the long overnight flight from London.
However, there seemed to be a promising outlook for midfielder Gareth Barry, who was recovering from an injured right ankle.
"He is getting better and better every day. He started training with the team. He will go to the gym this afternoon with the physiotherapist and always train with the team in the mornings," said Capello before adding that he was unsure if Barry would feature in England's opening match against the US.
"He will not do everything just yet and we have to be a little careful with him just at this moment."
The England manager added that he was thrilled to be in South Africa and was revelling in finally having a serious game to prepare for. "It is seven months now since our last qualifying game," he added.
Ferdinand took over as England captain after fellow defender John Terry was stripped of the job in February because of an off-pitch scandal involving his private life but he has not played regularly for Manchester United this season due to a succession of injuries.
He played for England in the 2002 and 2006 World Cup finals and has made a total of 78 appearances, scoring three goals.