Jack Nowell and Sam Underhill will play no part in England's Six Nations match against France after suffering injuries in training, while captain Dylan Hartley could also miss out.
Exeter Chiefs wing Nowell has been ruled out of the remainder tournament following an ankle injury, with Underhill having sustained a toe problem.
The Bath forward has a chance of being fit for the showdown with Ireland in the final round.
England's forwards coach Steve Borthwick told the BBC that Hartley will be "monitored on a daily basis" before a decision is taken on his involvement, the Northampton Saints hooker having experienced muscle tightness in his leg.
Eddie Jones' side were beaten by Scotland last time out, ending their hopes of achieving the Grand Slam ahead of Saturday's clash with France at Twickenham.