England lock George Kruis has been ruled out of the November internationals against Japan and Australia due to a calf injury.
The injury-plagued second row was replaced by Charlie Ewels in the 66th minute in the 16-15 defeat by New Zealand at Twickenham on Saturday, limping heavily as he left the field.
In his absence and with Joe Launchbury also missing, Maro Itoje is expected to line up alongside Courtney Lawes or Ewels against Japan, who are playing England at Twickenham for the first time.
England's Australian coach Eddie Jones retained a group of 30 players on Tuesday, including uncapped quartet Ted Hill, Nick Schonert, Elliott Stooke and Joe Cokanasiga, but there was again no place for fullback Mike Brown.
"George has got a calf injury. It's highly unlikely he'll be available again for a few weeks - anywhere from four to eight weeks," Jones later told reporters.
"It's a calf strain. He did it during the game. It's disappointing because he'd been out injured for a while and was just coming back into form.
"We'll certainly miss him, but it opens the door for Courtney Lawes or Charlie Ewels to come in. It's testing the depth of the squad."
Dylan Hartley is expected to be available despite being replaced at half-time against New Zealand because of a thumb injury, but Manu Tuilagi is unlikely to be risked as he builds fitness in the wake of a groin strain.
"Manu came in yesterday (Monday) and did a little bit of running," said Jones, who reiterated that he will name his strongest team for Saturday.
"But again, it's highly unlikely we'll risk him his week. If we can, we'll try to get him right for Australia."
Forwards: Charlie Ewels, Jamie George, Dylan Hartley, Alec Hepburn , Ted Hill, Maro Itoje, Courtney Lawes, Zach Mercer, Ben Moon, Nick Schonert , Brad Shields, Kyle Sinckler, Elliott Stooke, Sam Underhill, Harry Williams , Mark Wilson.
Backs: Chris Ashton, Joe Cokanasiga, Danny Care, Elliot Daly, Owen Farrell , George Ford, Alex Lozowski, Jonny May, Jack Nowell, Henry Slade, Ben Te'o, Manu Tuilagi, Richard Wigglesworth, Ben Youngs.
