Manu Tuilagi will miss England's Six Nations opener against Scotland on Saturday, the coach Stuart Lancaster has announced.
Tuilagi has been ruled out of the Twickenham encounter with an ankle injury but could return for the second round of the championship against Ireland the following weekend.
Lancaster also confirmed that the prop Alex Corbisiero will be sidelined for the entire Six Nations with a knee problem.
"Manu has run out of time for Scotland and we'll make a call on him for Ireland early next week," Lancaster said.
Tuilagi was impressive during last autumn's record 38-21 victory over the world champions New Zealand, scoring one try and creating two more.
"By the end of the week we expect Manu to be running fully and changing direction," Lancaster said. "The message I'm receiving from the medical team is that he will be training fully by Tuesday or Wednesday next week, but I'll need to make a call earlier in the week.
"Manu is a big loss – he was outstanding against New Zealand. But he missed the first two games of last year's Six Nations because of a hamstring and it's an opportunity for someone else.
"It's disappointing for him, but it's not a long-term injury so he'll be back soon."
England must decide whether to draft in Billy Twelvetrees or Jonathan Joseph to partner Brad Barritt, while the fly-halves Toby Flood and Owen Farrell are alternatives.
"We have a pretty good idea of how we'll rejig the midfield. We have our thoughts," Lancaster said.
"It changes the emphasis a little bit, but it won't fundamentally affect the way we play. Brad will be in the equation and we need to make sure we can still break the gain line and have physical defenders. We've got to have the ability to get across the gain line and defend."
Meanwhile, Scotland's interim coach Scott Johnson has confirmed that Kelly Brown will remain as captain for the game with England.
The flanker led the team during the autumn internationals and Johnson, who took over following the resignation of Andy Robinson last November, said he was happy for Brown to stay on, but did not confirm if the 30 year old would keep the role for the whole series.
"We believe Kelly has the qualities we're looking for to captain Scotland. Captaincy is about deed in my book, not Churchillian oratory, and the experience that Kelly brings to the Test match arena is good for this team," he said.