Darron Gibson replaces Jack Rodwell in the only change to the side that beat Crystal Palace 4-0 last weekend.
Rodwell picked up a hamstring injury at Selhurst Park and Moyes has opted for Gibson ahead of the fit again Steven Pienaar.
He is on the bench alongside Wahbi Khazri and Fabio Borini.
Joleon Lescott and Adnan Januzaj are both fit to start as expected.
Sunderland XI: Mannone, Jones, Kone, O'Shea, Denayer, Oviedo; Gibson, Larsson, Ndong; Januzaj, Defoe
Subs: Mika, Manquillo, Borini, Pienaar, Khazri, Lescott, Honeyman
Southampton XI: Forster, Cedric, Stephens, Yoshida, Bertrand; Romeu, Davis, Ward-Prowse; Tadic, Redmond, Gabbiadini
Subs: Hassen, Gardos, McQueen, Hojbjerg, Sims, Long, Rodriguez