The 27-year-old Germany international sat out of the weekend FA Cup fixture and has been contenting with a slight foot injury in recent weeks.
Ozil has 16 assists in the Premier League this season and is just four assists away from matching Henry’s record record tally of 20.
Arsenal defeated Burnley over the weekend and will be looking to return to winning ways in the league.
Arsenal confirmed line-up: Cech, Bellerin, Gabriel, Koscielny, Monreal, Flamini, Ramsey, Campbell, Ozil, Alexis, Giroud
Subs: Ospina, Chambers, Mertesacker, Gibbs, Coquelin, Oxlade-Chamberlain, Walcott
Southampton confirmed line-up: Forster; Cedric, Van Dijk, Fonte, Bertrand; Romeu, Ward-Prowse, Wanyama, Mane, Tadic, Long