Vice-captain Courtney Lawes will miss the rest of England's Six Nations campaign with a shoulder injury.
The Northampton forward made his long-awaited return off the bench against Wales but has now been hit by another setback.
Meanwhile, fly-half Marcus Smith has been retained in the 27-man squad, with George Ford going back to Sale.
It means Smith is set to feature against France on Saturday despite being released from camp last week.
England squad
Forwards: Ollie Chessum, Dan Cole, Ben Curry, Alex Dombrandt, Ben Earl, Ellis Genge, Jamie George, Nick Isiekwe, Maro Itoje, Lewis Ludlam, David Ribbans, Kyle Sinckler, Mako Vunipola, Jack Walker, Jack Willis.
Backs: Henry Arundell, Owen Farrell, Ollie Lawrence, Max Malins, Joe Marchant, Alex Mitchell, Henry Slade, Marcus Smith, Freddie Steward, Manu Tuilagi, Jack van Poortvliet, Anthony Watson.
Ford's inclusion over Smith during the fallow week suggested the former would be preferred in the matchday squad to face France.
However, assistant coach Kevin Sinfield said Smith benefited from the gametime for his club Harlequins, with the selection call made on Tuesday afternoon to include him in the squad.
"We've got three world-class 10s, and we felt it was the right thing for Marcus to get some minutes," Sinfield told BBC Sport.
"The balance for us is trying to get the makeup of a squad right each week, so that we've got everyone fit to train on a Monday and also make sure we look after players in the right way, and sometimes that is conflicting.
"We all feel it was the right thing for Marcus to go back and play, and he was outstanding, wasn't he?
"I think for him to play like he did means he is massively in the mix."
"He's come back with a spring in his step, which is good for us," added captain Owen Farrell.
Sinfield says Ford has been "outstanding" in camp and had been in contention to face France after a long lay-off with an Achilles tendon injury.
"He is sharp. I have no doubt George would say he is ready, and watching him in training and watching him compete you would have to say he is ready," Sinfield added.
"But we can't keep all three here, one of them needs to go away and play, and we decided this week it was going to be George."
Sinfield also confirmed Lawes would play no further part in the Championship after suffering a shoulder injury in the gym.
After captaining England to a series victory in Australia Lawes has been sidelined by concussion, glute and calf problems.
"We are waiting for a full report, but unfortunately he will miss the rest of the campaign for us," Sinfield said.
"It has been a tough old season for him, but he'll be back."
England host France on Saturday before a final-day showdown with Grand Slam chasing Ireland in Dublin.