Owen Farrell will miss the entire Six Nations with a knee injury he suffered while on duty for Saracens.
Farrell picked up the injury, which is being described as a high-grade medial ligament strain, in Sunday's European Champions Cup match at Clermont. It's not known at this stage how long he'll be ruled out for.
George Ford, who started England's final two Tests in November, is now set to start the Six Nations opener against Wales, with Stephen Myler and Danny Cipriani competing for a spot on the bench.
Centre Brad Barritt and lock Geoff Parling remain major doubts to make the game due to knee medial ligament strains. England are also waiting on Tom Wood (ankle) and Kyle Eastmond (shoulder).
'It's a real shame for Owen that he sustained this injury and we wish him the best for his recovery,' Stuart Lancaster said. 'We are fortunate to have three other No 10s in the squad in what is a very competitive position and we will look forward to seeing how they go over the Six Nations.
'We will continue to assess and treat the other players' injuries and will provide an update at the launch tomorrow.'
Photo: Adrian Dennis/AFP Photo