Mark Hughes' side, like Chris Hughton's, have won one, drawn one and lost two in what has been a mixed start to the season for both teams, so this one will be tough to call.
Both teams have natural goalscorers in Glenn Murray, Charlie Austin and Danny Ings, so whether or not they bring their A game may determine the outcome of this south coast clash.
1. Goalkeeper & Defenders
Mathew Ryan (GK) - The Australian international will start.
Martin Montoya (RB) - The Spaniard, a summer signing from Valencia, has started his Brighton career well and will retain his place.
Shane Duffy (CB) - The formidable partnership of Shane Duffy and Lewis Dunk will, of course, line up alongside each other once again.
Lewis Dunk (CB) - Dunk, perhaps Brighton's star man, will start as he does most weeks.
Gaetan Bong (LB) - Gaetan Bong will make up the rest of Chris Hughton's backline.
Dale Stephens (CM) - Brighton's midfield lynch-pin is arguably one of the Seagulls' most important players and is pivotal to their success.
Davy Propper (CM) - The Dutchman will start in a two man midfield with the aforementioned Stephens.
Anthony Knockaert (RM) - Brighton's biggest attacking threat will look to take the game to Southampton from the right side of midfield.
Solly March (LM) - Brighton's left midfielder has been a bright spark this season with his direct dribbling.
Pascal Groß (CAM) - The German has been Brighton's star man since his arrival last summer, and any chances of a win against the Saints may rest on his shoulders.
Glenn Murray (ST) - The evergreen Glenn Murray has already scored three goals this season and looks to be getting better with age.