Steven Davis does not make the squad having come off injured in the 1-0 EFL Cup victory over Liverpool on Wednesday and is replaced by James Ward-Prowse. Jordy Clasie, who was also substituted in midweek but is fit enough for the bench, is replaced by Pierre-Emile Hojbjerg, while Shane Long spearheads the attack in place of Jay Rodriguez.
Virgil van Dijk again captains the team as wantaway Jose Fonte sits out once more.
For Burnley, mass changes see George Boyd, Jeff Hendrick, Matthew Lowton, Ben Mee, Dean Marney, Ashley Barnes and goalkeeper Tom Heaton come into the XI, while defender Jon Flanagan graces the bench having been out injured since Boxing Day.
Johann Berg Gudmundsson and Scott Arfield are both unable to take part after picking up hamstring injuries against Sunderland in the FA Cup.
Burnley: Heaton; Lowton, Keane, Mee, Ward; Hendrick, Defour, Marney, Boyd; Barnes, Gray
Subs: Flanagan, Kightly, Darikwa, Vokes, Robinson, Tarkowski, Barton
Southampton: Forster; Soares, Van Dijk, Yoshida, Bertrand; Romeu, Hojberg; Tadic, Ward-Prowse, Redmond, Long
Subs: Taylor, Clasie, Rodriguez, Martina, Reed, Stephens, Sims