Ireland coach Eddie O'Sullivan confirmed: "Brian has a hamstring tear that he picked up in a ruck. It's happened to him before.
"He was in the approach position, his foot slipped and he was hit from behind. It will certainly take him out of the England game."
The injury capped off a disappointing day for O'Driscoll's side and cuts down on Ireland's midfield options for the England game - his long-time centre partner Gordon D'Arcy broke his arm against Italy last month.
O'Driscoll is due to have a scan on his hamstring tomorrow (Monday) and an update on his condition will be issued afterwards.
O'Sullivan said he does not see his skipper as a doubt for Ireland's summer tour to New Zealand and Australia. Their opener is against the All Blacks in Wellington on June 7.
"I don't think Brian will miss out against the All Blacks and Wallabies," O'Sullivan said on Sunday.
"We don't know how bad the injury is but talking to him last night I don't think it's too serious. But the only real proof will be in the scan.
"I think he'll be gone for six to eight weeks, but that's a guess. This is the third time he's endured the exact same injury. He got it in Rome three years ago and also for Leinster during a Heineken Cup game."