Arsenal's Henrikh Mkhitaryan (knee) is out of the match on Sunday after being injured in the UEFA Europa League victory over CSKA Moscow.
David Ospina (ankle) has been sidelined for two to three weeks and Ainsley Maitland-Niles is also out.
Southampton have reported no fresh injury concerns for their trip to Emirates Stadium.
Did you know?
If Arsenal win, it will be their 150th Premier League victory at Emirates Stadium out of 226 matches. They'll be the only side to have won 150+ matches at two different stadiums in the competition.
Charlie Austin has scored five goals in his six starts in the PL for Southampton this season. He's also scored in all three of his PL matches against the Gunners, the joint-best 100 per cent record against them in the competition with Mohamed Salah and Callum Wilson.
The Gunners are unbeaten in their last 22 home league games against Southampton, since a 0-1 defeat in November 1987.
Mark Hughes has already beaten Arsenal with Stoke this season, back in August. He could become the first manager to beat them twice in the same PL season with two different clubs.
Club previews
Arsenal: Mkhitaryan injury latest
Southampton: Saints get set for Arsenal
Referee: Andre Marriner
Assistants: Scott Ledger, Simon Long
Fourth official: Mike Dean