England lock Geoff Parling has been ruled out of Saturday's opening QBE International against Australia with concussion.
Parling was concussed during a contact session at the squad's Pennyhill Park training base on Tuesday afternoon and will undergo the recommended graduated return to play protocol.
England head coach Stuart Lancaster said: "Geoff will be unavailable for Saturday's game but will stay in camp with a view to returning to training next week."
Parling would have been involved in the matchday 23 against Australia and was competing with Courtney Lawes and Joe Launchbury for a place in the starting XV.
The British and Irish Lion's absence has simplified what was proving to be one of the most difficult selection calls for Lancaster.
Lawes and Launchbury are now likely to start with Bath's Dave Attwood, who only returned from a rib injury last week, supplying cover from the bench.
Lancaster has released 11 players back to their clubs for Aviva Premiership duty this weekend, leaving him with a 23-man squad from which his starting line-up will be announced on Thursday morning.
Ben Foden looks to be included on the bench at Twickenham on Saturday after Alex Goode was sent back to Saracens with Chris Ashton, Marland Yarde and Mike Brown forming the back three.
The starting centre combination will be Billy Twelvetrees and Joel Tomkins as Henry Trinder, Luther Burrell and Kyle Eastmond will be on club duty this weekend.
They are joined by Danny Care, leaving Lancaster to choose between Ben Youngs and Lee Dickson at scrum-half in what is probably the only position causing a selection headache now that the second-row conundrum has been solved by Parling's injury.
"It's never easy deciding who to select and that's what you want - players pushing hard for places across the board," Lancaster said.
"We have had two good days of training here at Pennyhill Park and, added to last week in Leeds, we are in good form and looking forward to the game."
England squad to face Australia:
David Attwood (Bath Rugby)
Dan Cole (Leicester Tigers)
Dylan Hartley (Northampton Saints)
Joe Launchbury (London Wasps)
Courtney Lawes (Northampton Saints)
Joe Marler (Harlequins)
Ben Morgan (Gloucester Rugby)
Chris Robshaw (Harlequins)
Billy Vunipola (Saracens)
Mako Vunipola (Saracens)
David Wilson (Bath Rugby)
Tom Wood (Northampton Saints)
Tom Youngs (Leicester Tigers)
Chris Ashton (Saracens)
Mike Brown (Harlequins)
Lee Dickson (Northampton Saints)
Owen Farrell (Saracens)
Toby Flood (Leicester Tigers)
Ben Foden (Northampton Saints)
Joel Tomkins (Saracens)
Billy Twelvetrees (Gloucester Rugby)
Marland Yarde (London Irish)
Ben Youngs (Leicester Tigers)
Alex Corbisiero (knee) and Geoff Parling (mild concussion) will also return to camp for continued treatment.
Players released: F Burns (Gloucester), L Burrell (Northampton), D Care (Harlequins), K Eastmond (Rugby), A Goode (Saracens), T Johnson (Exeter), M Kvesic (Gloucester), H Thomas (Sale), H Trinder (Gloucester), R Webber (Bath), C Wade (Wasps).