Ben Stokes will undergo surgery on a torn hamstring and be out of action for at least three months.
The England captain was injured during the recent third Test against New Zealand in Hamilton, a series which England won 2-1.
“Ben Stokes has been ruled out of all cricket for at least three months after further assessments confirmed he has torn his left hamstring,” said an England and Wales Cricket Board spokesperson.
“The Durham all-rounder will undergo surgery in January.”
Stokes had been left out of England’s squad for the Champions Trophy in February and March when the 15-man party was announced on Sunday.
Despite his presence against New Zealand, the 33-year-old had previously missed the summer series against Sri Lanka and the first Test against Pakistan in the autumn due to hamstring issues.
He insisted later there will be no “holding back” when he recovers from his latest injury problems, insisting he is ready to keep digging deep for England.
Stokes said: “Every setback, I come back stronger.
“There’s no doubt I’ll be going away from here, working my arse off as I always do and getting myself back to where I was. That’s my job.”