The Saints' full-back has been forced to pull out of the European Championship play-off against Serbia due to a leg injury sustained in the 2-2 draw with Fulham last weekend
England Under-21 defender Nathaniel Clyne has withdrawn from the squad for their vital Euro 2013 play-off with Serbia.
The 21-year-old sustained a dead leg in the defeat against Everton, which kept him out of the Saints' dramatic 2-2 draw with Fulham last weekend and has failed to recover in time.
Southampton boss Nigel Adkins confirmed Clyne's absence, however the injury is not thought to be overly serious and should not keep him out of action following the international break.
Adkins told reporters: "Nathaniel has a dead leg that he picked up at Everton and had to come off which he hasn't recovered from. I would suggest that as he hasn't played (on Sunday), he won't be fit to go away with England."
Clyne is the second player to withdraw from the squad, after Nottingham Forest midfielder Henri Lansbury also pulled out due to injury. Liverpool defender Jack Robinson has been called into the squad as a replacement.
Manager Stuart Pearce will also have to cope without midfielder Jonjo Shelvey and Chelsea full-back Ryan Bertrand after they were both called into the senior squad for their World Cup qualifiers against San Marino and Poland because of an injury to Arsenal's Kieran Gibbs.