Aston Villa manager Paul Lambert has reshuffled his team following Tuesday's Capital One Cup semi-final first-leg defeat to Bradford City.
Brad Guzan returns in goal, while Enda Stevens comes in for Joe Bennett at full-back.
Brett Holman and Ashley Westwood also feature in the Villans' starting XI, with Barry Bannan and Gabriel Agbonlahor making way.
Meanwhile, Nigel Adkins makes three changes to the side that lost at home to Chelsea in the third round of the FA Cup.
Jos Hooiveld, Gaston Ramirez and Nathaniel Clyne come in for Jose Fonte (knee), Guly do Prado (illness) and Steven Davis.
Villa: Guzan; Clark, Stevens, Baker, Lowton; Holman, Weimann, Westwood, Delph, N'Zogbia; Benteke
Southampton: Boruc, Clyne, Yoshida, Hooiveld, Shaw, Puncheon, Schneiderlin, Cork, Ramirez, Lambert, Rodriguez
Michael Penkman
