The Gunners are travelling to Southampton again on Tuesday, this time in the Premier League, and will be hoping to bounce back from the weekend’s loss.
Kieran Tierney has been struggling with a calf issue and misses out, while David Luiz comes back into the side.
In midfield, Thomas Partey starts and ahead of him Bukayo Saka and Emile Smith Rowe also play.
Nicolas Pepe gets a start ahead of Gabriel Martinelli on the left wing as Pierre-Emerick Aubameyang has been ruled out due to “personal family reasons”.
Alexandre Lacazette comes in for Eddie Nketiah to lead the attack.
Dani Ceballos and Pablo Mari have been struggling with calf issues and will not be fit in time.
Arsenal XI: Leno, Bellerin, Holding, Luiz, Cedric, Thomas, Xhaka, Pepe, Smith-Rowe, Saka, Lacazette
Subs: Gabriel, Willian, Maitland-Niles, Chambers, Elneny, Willock, Nketiah, Ryan, Martinelli
Tuesday 8.15pm GMT, BT Sport
Venue: St. Mary’s Stadium
Arsenal squad from: Leno, Runarsson; Bellerin, Cedric, Chambers, Gabriel, Holding, Luiz, Mustafi, Tierney; Elneny, Maitland-Niles, Partey, Saka, Smith Rowe, Willock, Xhaka; Aubameyang, Balogun, Lacazette, Martinelli, Nelson, Nketiah, Pepe and Willian.
Injured: Ceballos (calf), Mari (calf)