Wigan goalkeeper Chris Kirkland has followed Chelsea's Wayne Bridge out of the England squad through injury ahead of Wednesday's friendly clash with Spain.
Bridge's injury is likely to come as a major worry for Blues boss Jose Mourinho, who has recently lost the services of his other England left-back, Ashley Cole, for most of the remainder of the campaign.
Bridge limped out of England training after just 15 minutes at Carrington on Monday, due to a thigh strain.
The 26-year-old seemed certain to win his 25th cap in midweek but has now returned to Stamford Bridge for treatment, with Mourinho no doubt desperately hoping the damage is not too serious.
Bridge's injury is likely to give Aston Villa's Gareth Barry a chance to start at left-back on his return to the international fold.
Kirkland has been forced out with a shoulder injury, while Andy Johnson dropped out earlier on Monday after making his return to Premiership action at Liverpool on Saturday. Jermaine Jenas (ankle) had already been ruled out, while Owen Hargreaves confirmed he will play no part in the fixture as he continues his rehabilitation from a broken leg.
There was some good news for England boss Steve McClaren though, with Wayne Rooney cleared to join up with the squad despite limping off in Manchester United's win at Tottenham on Sunday.
Meanwhile, Manchester City's Joey Barton could make his international debut against Spain, but his involvement is almost certain to be limited to that of substitute, with Steven Gerrard, Frank Lampard and Michael Carrick set to keep their places.