West Ham duo Fabian Balbuena and Javier Hernandez failed fitness tests ahead of the game at St Mary’s.
Aaron Cresswell is back for the Hammers, who are without a number of players, including Marko Arnautovic, and have named only six substitutes.
Cresswell’s inclusion is one of five changes made by boss Manuel Pellegrini.
Southampton make just one change, with the suspended Pierre-Emile Hojbjerg being replaced by Mario Lemina.
Southampton: McCarthy, Targett, Bednarek, Vestergaard, Yoshida, Valery, Romeu, Lemina, Armstrong, Remond, Ings.
Subs: Gunn, Stephens, Long, Austin, Elyounoussi, Ward-Prowse, Ramsay.
West Ham: Fabianski, Cresswell, Ogbonna, Diop, Antonio, Rice, Obiang, Snodgrass, Anderson, Diangana, Perez.
Subs: Adrian, Carroll, Noble, Masuaku, Silva, Coventry.