Ozil sat out of the weekend FA Cup fixture and has been contenting with a slight foot injury in recent weeks.
The Germany international 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.
The north London based club currently find themselves in third place in the league following a defeat to Chelsea last weekend. Arsenal are just two points above rivals Tottenham who sit in forth place.
Arsenal probable line-up: Cech, Monreal, Koscielny, Mertesacker, Bellerin, Ramsey, Flamini, Ozil, Sanchez, Walcott, Giroud
Southampton probable line-up: Forster; Cedric, Van Dijk, Fonte, Bertrand; Romeu, Clasie, Wanyama, Mane, Tadic, Long