England centre Brad Barritt and flanker Tom Croft are out of the Six Nations after suffering injuries on club duty.
Saracens’ Barritt, who hurt his ankle on Sunday, has not played for England since victory over Australia in the autumn after suffering calf and knee injuries but was in line for a recall.
Flanker Croft dislocated his shoulder playing for Leicester at the weekend.
Mike Brown, Tom Wood and Courtney Lawes are in line for selection after recovering from injury.
Championship-chasing England host Scotland on Saturday (17:00 GMT), before facing France at Twickenham a week later.
England are set to name an unchanged midfield after Barritt, who was challenging Luther Burrell for a place, was ruled out but have called Exeter Chiefs’ Henry Slade, 21, into the training squad as cover.
Inside centre Burrell was a doubt himself after suffering a calf injury in the19-9 defeat by Ireland but is set to resume training on Tuesday as head coach Stuart Lancaster finalises his team selection.
Elsewhere, full-back Brown has been cleared for a return after taking full part in training for the first time since suffering concussion against Italy three weeks ago.
Second-row Lawes completed his second game for Northampton Saints at the weekend following the ankle surgery which forced him to miss the opening three Six Nations matches.
“We’ve lost one or two lads with injuries which is a real disappointment, Croft and Barritt in particular,” head coach Stuart Lancaster told BBC Radio 5 live.
“That changes your thinking a bit, but I thought there were some good performances at the weekend and, more importantly, we’ve got two or three senior players coming back into the equation who we know have performed for us in the past.”
Lancaster said he was disappointed England’s destiny was no longer in their control after the Ireland loss.
England need to beat Scotland and hope Wales beat leaders Ireland in Cardiff to leave all three teams level on six points going into the final round.
“We were disappointed in ourselves. We knew that if we could have got a win in Ireland we would have two home games and an opportunity to win something. We’ve not achieved so that was the real frustration,” added Lancaster.
Flanker Chris Robshaw was criticised by some after the loss in Dublin, which ended England’s hopes of a first Grand Slam since 2003, but Lancaster defended his captain.
“We didn’t dominate the space beyond the ball as well as Ireland did,” he said. “Collectively we underperformed at the breakdown and I don’t think to single one player out is fair.”