Watford striker Troy Deeney starts on the bench for the Hornets after serving his four-match ban.
The Englishman was banned after being sent off for a dangerous challenge against Huddersfield Town, and the Hornets failed in their appeal of the charge.
Manager Marco Silva opts for a front three of Richarlison, Andre Gray and Andre Carrillo.
As for Southampton, centre-back Wesley Hoedt returns from a spell out with concussion, while Jeremy Pied has shrugged off a leg problem and is fit enough for the bench.
Watford: Gomes; Zeegelaar, Kabasele, Wague, Janmatt; Watson, Cleverley, Doucoure; Richarlison, Gray, Carrillo
Subs: Karnezis, Prodl, Mariappa, Deeney, Holebas, Okaka, Pereyra
Southampton: McCarthy; Cedric, Stephens, Hoedt, Bertrand; Hojbjerg, Ward-Prowse, Romeu, Davis, Tadic; Long
Subs: Forster, Pied, Bednarek, Lemina, Boufal, Sims, Gabbiadini
More to follow.
