Care will undergo surgery this week after damaging a joint in his left big toe in last weekend's 19-9 defeat to Wales.
England medics anticipate Care will be sidelined for six weeks, ruling him out of the initial 30-man World Cup squad to be announced by manager Martin Johnson on August 22.
Johnson said: "We are all hugely disappointed for Danny who has worked extremely hard and has been an important part of the squad throughout our Rugby World Cup preparations.
"He featured in both warm-up fixtures and was on course for selection so this injury is really disappointing for him personally and for us as a squad.
"Nobody wants to see a player ruled out at this stage through injury and we all wish Danny a speedy recovery.
"In terms of our selection options we are fortunate to have depth at nine with Ben Youngs, now back into full training, Joe Simpson and Richard Wigglesworth.
"These guys have all been part of the Rugby World Cup camp and will be considered ahead of the final 30 man squad announced on Monday."
Care was the form scrum-half in England at the end of last season and he had mounted a strong case to reclaim the England nine jersey from Ben Youngs with his performances in the two warm-up internationals against Wales.
Youngs did not feature in either match but he is back in training after undergoing a knee operation at the end of last season.
Wigglesworth, who enjoyed an impressive season with Aviva Premiership champions Saracens, started last Saturday's game in Cardiff but was replaced after half an hour having suffered a blow to the head.
Care came off the bench to replace him and enhanced his own World Cup credentials in an otherwise disappointing England performance - only to damage his toe at the same time.
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