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Sam Allardyce has been forced to make four changes to the side that drew 1-1 with Manchester United, as Mark Noble and Kevin Nolan are both ruled out.
It means that Carlton Cole and Morgan Amafitano earn a starting berth, as Allardyce opts for a 4-3-3 formations at St Marys.
For the Saints, Morgan Schneiderlin misses out for the hosts through injury, while new signing Filip Djuricic starts on the bench.
TEAMS IN FULL
Southampton starting XI: Forster, Clyne, Fonte, Gardos, Yoshida, Wanyama, Reed, S. Davis, Mané, Elia, Pellè.
Substitutes: K. Davis, Tadić, Djuričić, Ward-Prowse, McCarthy, Flannigan.
West Ham starting XI: Adrian, Jenkinson, Tomkins, Kouyate, Cresswell, Song, Amafitano, Downing, Valencia, Sakho, Cole
Substitutes: Jaaskelainen, Burke, Oxford, O'Brien, Jarvis, Carroll, Lee
Speaking after West Ham's draw with Manchester United at the weekend, Allardyce admitted his side were 'gutted' following Daley Blind's late equaliser.
"The lads are absolutely gutted in there and so they should be," Allardyce told Sky Sports.
"I think it was an absolutely fantastic performance and from the point of view of where we were just towards the end (of the match), I thought we were going to make sure we saw it through and unfortunately for us it was not to be."
Allardyce added: "I suppose in the end we couldn't cope with long-ball United. It was just, 'thump it forward and see what they could get' and in the end it paid off for them."
