Centre Ben Te'o has been ruled out of England's Six Nations match with Ireland on Saturday with a side strain.
The Worcester player picked up the injury in training in Portugal this week and will not travel to Dublin.
Meanwhile, Wasps flanker Brad Shields will also miss the game at the Aviva Stadium, as will Bath wing Joe Cokanasiga.
Te'o's absence means Manu Tuilagi is in strong contention to make his first England start since 2014.
The 27-year-old Leicester centre returned to the international fold at the end of November, coming off the bench as England overwhelmed Australia at Twickenham.
He says he is physically and mentally primed to make an impact this Six Nations after an injury-ravaged few years.
"I'm in a good place. If your mind is positive you will go forward from there," Tuilagi told BBC Sport.
"I'm fit and healthy - touch wood - and just enjoying being back.
"It's definitely as fit as I have ever been and everything is going well so far. It's all about enjoyment for me."
The England management hope Te'o will be available for the France game on the second weekend of the Championship, but his absence on Saturday leaves a physical void in the midfield, which Tuilagi is set to fill.
England boss Eddie Jones has the option of reuniting George Ford and Owen Farrell in the midfield alongside Tuilagi, or pairing Tuilagi and Henry Slade at centre, with captain Owen Farrell at fly-half.
Shields' absence in the back row means Mark Wilson is set to start on the blind-side flank, with Tom Curry at open-side and the fit-again Billy Vunipola at number eight.
"We have some more training today [Tuesday] and tomorrow [Wednesday], and then we will finalise selection after that," said assistant coach Neal Hatley.
Twenty five players are in contention to feature against Ireland, with Jones naming his match-day squad and starting XV on Thursday morning.
Forwards: Luke Cowan-Dickie (Exeter Chiefs), Tom Curry (Sale Sharks), Ellis Genge (Leicester Tigers), Jamie George (Saracens), Nathan Hughes (Wasps), Maro Itoje (Saracens), George Kruis (Saracens), Joe Launchbury (Wasps), Courtney Lawes (Northampton Saints), Kyle Sinckler (Harlequins), Billy Vunipola (Saracens), Mako Vunipola (Saracens), Harry Williams (Exeter Chiefs), Mark Wilson (Newcastle Falcons)
Backs: Chris Ashton (Sale Sharks), Mike Brown (Harlequins), Elliot Daly (Wasps), Owen Farrell (Saracens) captain, George Ford (Leicester Tigers), Jonny May (Leicester Tigers), Jack Nowell (Exeter Chiefs), Dan Robson (Wasps), Henry Slade (Exeter Chiefs), Manu Tuilagi (Leicester Tigers), Ben Youngs (Leicester Tigers)