England manager Fabio Capello has a selection headache after John Terry and Ashley Cole were ruled out of the World Cup qualifier against Belarus on Wednesday.
The Chelsea defenders are both injured - Terry with a long-standing back injury and Cole with a hamstring complaint.
Neither man will travel to Minsk with the squad on Tuesday, and will return to their club.
"It's disappointing to lose two very experienced players in John Terry and Ashley Cole for the game in Belarus," said Capello.
"Unfortunately they have no chance of playing, so it is best they return to Chelsea."
Cole was booed by the Wembley crowd during England's 5-1 win against Kazakhstan on Saturday after an error that led to the visitors' goal. He completed 90 minutes and showed no sign of injury.
His absence will surely lead conspiracy theorists to suggest that Capello has withdrawn the left-back to protect him from further abuse.
Cole's Chelsea colleague Wayne Bridge is expected to deputise, although Everton's Joleon Lescott is another option to play left-back.
Rio Ferdinand will continue to captain the side in Terry's absence, having done so against Kazakhstan.
Terry performed light training and gym work on Sunday but failed to come through rigorous tests on Monday morning.
Capello has hinted that Terry's absence could lead him to continue to deploy Gareth Barry as a holding midfielder.
Speaking after Saturday's game, Capello said: "I have time to decide whether to play a holding midfielder in Belarus. First we have to wait and see whether John Terry will play, then we will decide about the midfield.''
England lacked cohesion and drive in the first half with Barry, Steven Gerrard and Frank Lampard in a three-man midfield.
They registered a marked improvement following a half-time switch to 4-4-2 that saw Shaun Wright-Phillips come on for Barry.
England are top of Group 6 after winning their first three games. Belarus are fourth having played one game fewer. They lost 1-0 away to Ukraine, before winning 3-1 in Andorra.