Everton's Andrew Johnson has pulled out of the England squad for Wednesday's friendly with Spain at Old Trafford.
And he has been joined on the sidelines by Chelsea's Wayne Bridge, meaning either Phil Neville or Gareth Barry will start the match.
Goalkeeper Chris Kirkland has also been ruled out of the match with a shoulder injury. He will remain with his club instead of linking up with Steve McClaren's party.
The news is likely to mean a place on the bench for Manchester United's Ben Foster who has impressed in two seasons on loan at Watford.
Jermaine Jenas (ankle) had already withdrawn while Owen Hargreaves has confirmed he will not play in the final match before England's crucial Euro 2008 qualifier in Israel next month.
Johnson only returned to first team action with the Toffees in Saturday's Merseyside derby draw at Liverpool but does not feel his ankle injury has healed sufficiently to allow him to play against Spain.
England coach Steve McClaren already knew Johnson would be a bit part player at best and his confirmed absence could offer Kieron Dyer a chance to play under the new coach for the first time.
Johnson's absence is a blow given Wayne Rooney's fitness cannot be taken for granted even though the Manchester United man was cleared to link up with his international team-mates by the Red Devils this morning.
Rooney suffered an ankle injury in yesterday's win at Tottenham and will now be assessed by FA medical staff before a decision over his availability is taken.
If Rooney does miss out it will rob McClaren of his entire three-man strike force from the November draw in Holland.
Joe Cole is already out with a broken foot and Owen Hargreaves today revealed he will not play any part on Wednesday either.
Bayern Munich midfielder Hargreaves was named in the England squad despite only returning to action from a broken leg in Friday's Bundesliga defeat to Nuremberg.
He told BBC Sport: 'I spoke to England manager Steve McClaren on Saturday.
'He asked how the game was. I told him it was good but I was physically a bit tired and sore.
'That's why I'm not going to play against Spain.
'I just returned on Friday and to play again on Wednesday would be too much.'