The pair have slipped down the attacking pecking order in recent weeks following the rise of the likes of Emile Smith Rowe.
Mikel Arteta, however, has made changes for Saturday’s fourth round tie at St Mary’s and Pepe and Willian start.
Eddie Nketiah is another who is handed a start, while Gabriel Martinelli is also in from the off after returning to full fitness.
In midfield, Mohamed Elneny comes in but Dani Ceballos misses out entirely after a late fitness test on his own calf complaint.
Calum Chambers has hoped to get a rare start in defence, but is on the bench with Gabriel Magalhaes making his first appearance since recovering from Covid-19.
Arsenal opt against handing a debut to Mat Ryan after the goalkeeper joined on loan from Brighton. Bernd Leno gets the nod.
Southampton XI: Forster, Walker-Peters, Bednarek, Stephens, Bertrand, Diallo, Ward-Prowse, Armstrong, Walcott, Ings, Adams
Arsenal XI: Leno, Bellerin, Holding, Gabriel, Cedric, Elneny, Xhaka, Pepe, Willian, Martinelli, Nketiah
Saturday 12.15pm GMT, BBC
Venue: St Mary’s Stadium
Arsenal squad from: Leno, Runarsson; Bellerin, Cedric, Chambers, Gabriel, Holding, Luiz, Mustafi, Tierney; Ceballos, Elneny, Maitland-Niles, Partey, Saka, Smith Rowe, Willock, Xhaka; Aubameyang, Balogun, Lacazette, Martinelli, Nelson, Nketiah, Pepe and Willian.