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Shkodran Mustafi was forced off with a small thigh problem in the 3-1 defeat to Manchester United, though manager Arsene Wenger is still hopeful he could be available for the trip to Southampton.
Per Mertesacker is likely to be on standby to replace his compatriot, with Laurent Koscielny and Nacho Montreal appearing sure starters elsewhere in the three-man defence.
Hector Bellerin and Sead Kolasinac should continue in the wing-back roles in the 3-4-2-1 formation.
Granit Xhaka and Aaron Ramsey should continue in central midfield unless the Gunners boss looks to rotate given the congested schedule.
That seems unlikely at this point, though, as Wenger has been using fringe players in European fixtures to keep his regulars fresh for domestic duties.
Francis Coquelin, Mohamed Elneny and Jack Wilshere are the back-up options.
Mesut Ozil, Alexis Sanchez and Alexandre Lacazette should again form the front three, with Danny Welbeck, Alex Iwobi and Olivier Giroud the alternatives.
Santi Cazorla is a long-term absentee for the Gunners.