Manchester United duo Michael Carrick and Danny Welbeck have been ruled out of England's friendlies against Chile and Germany through injury.
Carrick carried an Achilles injury into United's 1-0 win over Arsenal and even though he completed 90 minutes at Old Trafford, he has withdrawn from the England squad.
Welbeck has not played since October 19 because of a knee injury and he has also pulled out of the double-header.
No replacements have been called up, leaving manager Roy Hodgson with 26 men to choose from for the friendly against Chile on Friday, and the visit of the Germans four days later.
England's preparations for the matches received a slight disruption when they were forced to change their hotel because of a virus at St George's Park.
The squad met up in Watford on Tuesday, rather than their normal base in Staffordshire, although the FA insists this was a precautionary measure.
No England players are understood to have been affected by the virus.
Positive news for Hodgson is that Liverpool captain Steven Gerrard (hip), Daniel Sturridge (foot) and Arsenal midfielder Jack Wilshere (ankle) have joined up with the squad despite their respective injury problems.
The squad will train at Arsenal's base in London Colney on Tuesday afternoon and Wednesday before they host Chile at Wembley on Friday night.
Carrick's withdrawal increases the likelihood of fellow midfielders Ross Barkley, Jordan Henderson, Tom Cleverley and Adam Lallana getting some game time against Chile.
Hodgson has always said he would use the two games as an opportunity to experiment with emerging players.
Welbeck's withdrawal also means Jay Rodriguez has a good chance of featuring against the South Americans, as Hodgson has already described the uncapped Southampton man as an ideal replacement for the Manchester United forward, who has been a regular under the current England boss.
Captain Gerrard has been troubled by a hip problem for the last couple of weeks and is expected to play just one of the two matches.
Frank Lampard, who will be awarded a commemorative 100th cap before the Chile game, may captain the side against Chile.
Lampard's two daughters, Luna and Isla, are understood to be mascots for the clash against the South Americans.