Theo Walcott misses out for Arsenal against his former club.
Gunners boss Arsene Wenger had suggested he was considering playing Walcott, but the player has been nursing a calf problem and is not even among the substitutes.
Alexis Sanchez, Mesut Ozil and Alexandre Lacazette all start for the visitors, while Jack Wilshere is on the bench.
Southampton make four changes, including the return of Nathan Redmond to their starting line-up.
Southampton: Forster, Van Dijk, Stephens, Yoshida, Bertrand, Hojbjerg, Romeu, Ward-Prowse, Radic, Redmond, Austin.
Subs: McCarthy, Hoedt, Davis, Lemina, Boufal, Gabbiadini, Pied.
Arsenal: Cech, Koscielny, Mertesacker, Monreal, Bellerin, Ramsey, Xhaka, Kolasinac, Ozil, Sanchez, Lacazette.
Subs: Ospina, Maitland-Niles, Iwobi, Wilshere, Coquelin, Giroud, Welbeck.