Courtney Lawes and George McGuigan have both been forced to withdraw from England's training squad for the Six Nations.
Vice-captain Lawes suffered a calf injury playing for Northampton Saints against La Rochelle in the Champions Cup on Saturday, while McGuigan has sustained a knee issue.
New coach Steve Borthwick has already lost Luke Cowan-Dickie to an ankle injury, with the hooker certain to miss at least the start of the tournament, while Jamie George suffered a concussion playing for Saracens in the Champions Cup on Sunday.
Tom Dunn and David Ribbans have been called up in place of Lawes and McGuigan.
England's Six Nations campaign begins against Scotland at Twickenham on February 4.