Anthony Watson may miss the whole of the Six Nations after England coach Eddie Jones ruled him out of next week's third-round match at home to Ireland.
The Bath wing was set to start in the tournament opener against France but was withdrawn the day before the team announcement because of a calf problem.
Watson also missed last Saturday's Calcutta Cup win away to Scotland and Jones has now confirmed he will be sidelined from the February 23 match with Grand Slam chasing Ireland at Twickenham as well.
"Anthony Watson is still a couple of weeks away," Jones told reporters at England's training base in London on Thursday.
After the Ireland match, England are at home to Wales on March 7 before the World Cup finalists finish their Six Nations campaign away to Italy a week later.
Watson, 25, has suffered with injuries for two years following successive Achilles problems and knee trouble.
The British and Irish Lion's last appearance for club or country was in Bath's 25-19 defeat by Harlequins on January 10.
Meanwhile Jones said centres Manu Tuilagi and Henry Slade could be fit to face Ireland.
Tuilagi suffered a groin strain against France but is on the verge of returning to full training, while Slade is nearing a full recovery from the ankle injury he sustained in late December.
"Manu is looking very good. Very promising. He should be in full training by the start of next week," Jones said.
"Henry Slade ran today (Thursday) and we've yet to get a medical report. It's definitely promising but too early to say whether he will be all right for Ireland or not," the Australian added.
England are currently fourth in the table, having been beaten 24-17 by France in Paris before defeating Scotland 13-6 at a windswept Murrayfield.
Still sidelined - England wing Anthony Watson