Chelsea interim manager Guus Hiddink has kept the same team that battered Manchester City's youngsters in the FA Cup last weekend.
That means Nemanja Matic and Oscar continue to sit on the bench, with John Obi Mikel and Pedro favoured.
Chelsea were ruthless in a 5-1 win at Stamford Bridge last week, and remain unbeaten under Hiddink.
For home side Southampton, unbeaten in six Premier League games, Ronald Koeman has made two changes to the team that beat Swansea City on 13 February.
The Saints have not played since then, but Koeman has brought in Charlie Austin for Graziano Pelle and Steven Davis coming in for James Ward-Prowse.
Southampton: Forster, Cedric, Fonte, Van Dijk, Bertrand, Targett, Clasie, Romeu, Davis, Austin, Long.
Subs: Stekelenburg, Yoshida, Mane, Tadic, Martina, Ward-Prowse, Pelle.
Chelsea: Courtois, Azpilicueta, Cahill, Ivanovic, Rahman, Mikel, Fabregas, Pedro, Willian, Hazard, Diego Costa.
Subs: Begovic, Matic, Loftus-Cheek, Kenedy, Oscar, Traore, RemyReuse content