The Saints skipper has not featured for the side since January due to an ankle injury and made an unsuccessful attempt to leave the club over the summer, submitting a transfer request just six weeks ago.
The Eagles, meanwhile, have a new manager in the shape of Roy Hodgson, who replaced Frank de Boer as boss on Tuesday after the club's dismal start to the season which has seen them lose all four games without scoring.
Hodgson has said that he was encouraged by what he saw in Palace's last game, a 1-0 defeat at Burnley, which saw the side dominate the encounter but lose out due to a third-minute goal from Chris Wood after a mistake from Lee Chung-yong.
Lee is duly dropped by Hodgson in just one change from that game against the Clarets, with a fit-again Ruben Loftus-Cheek coming back into the side alongside Andros Townsend and Christian Benteke up front.
James McArthur, Yohan Cabaye and Jason Puncheon continue in midfield, while there is an unchanged back four of Joel Ward, Timothy Fosu-Mensah, Scott Dann and Jeffrey Schlupp ahead of Wayne Hennessey between the posts.
Crystal Palace: Hennessey; Ward, Fosu-Mensah, Dann, Schlupp; McArthur, Cabaye, Puncheon; Townsend, Loftus-Cheek, Benteke
Subs: Speroni, Van Aanholt, Milivojevic, Tomkins, Lee, Sako, Kelly
Southampton: Forster; Soares, Yoshida, Hoedt, Bertrand; Romeu, Lemina; Tadic, Davis, Redmond; Long
Subs: McCarthy, Stephens, Van Dijk, Targett, Ward-Prowse, Boufal, Gabbiadini
Keep up with all of the action from Selhurst Park this afternoon with Sports Mole's live text commentary here.