A player that could have been at Newcastle in January, Matt Targett, will miss the game for the home side. The full-back has not featured this season.
Virgil Van Dijk had a very eventful summer, but was forced to stay at St Mary’s at the end of August. After not being in the team for the opening few weeks, the Dutchman has returned to the XI, and will start again on Sunday. He is likely to be paired with Maya Yoshida once again, with Wesley Hoedt still adapting to the English game.
The full-backs will definitely be Cedric Soares and Ryan Bertrand. In those two, Southampton have arguably the best pair in the division.
Dusan Tadic will be the one to offer the creative spark that his team have lacked so far this season. After clinching World Cup qualification during the break, the Serbian will be full of confidence heading into the weekend.
Nathan Redmond has also had a very poor start to the season, but is likely to start once again, as Mauricio Pellegrino refuses to give Sofiane Boufal a proper run in the team.
Manolo Gabbiadini burst onto the scene with excellent displays last season, but has struggled for goals (2) ever since the 2017 Capital One Cup final. The Italian may find himself on the bench again this week, with Charlie Austin back to full fitness.
Rafa Benitez also has an almost fully-fit squad to choose from. Only Paul Dummett and Massadio Haidara will miss the game. Both are long-term absentees.
Florian Lejeune has not played at all for the Magpies since the opening day, but may fancy his chances of getting a start, after a grueling international break for Ciaran Clark.
Chancel Mbemba could also return at left-back, although Javier Manquillo and Jesus Gamez are also options.
The big decision Benitez must make is whether or not to continue with Jonjo Shelvey an Mikel Merino in the midfield. The two looked very impressive against Liverpool, but away from home, Benitez may fancy starting the more defensive Isaac Hayden.
Ayoze Perez has been praised for his work rate this week by his manager, and will undoubtedly keep his place behind the striker.
That striker will probably be Joselu. The Spaniard got his second Newcastle goal in that draw with Liverpool and will look to use that renewed confidence here.
Aleksandar Mitrovic and Dwight Gayle are also available, but one of the two will ultimately be left out of the matchday squad entirely.
Southampton: Forster, Soares, Van Dijk, Yoshida, Bertrand, Romeu, Lemina, Davis, Tadic, Austin, Redmond
Newcastle: Elliot, Yedlin, Lascelles, Clark, Mbemba, Shelvey, Hayden, Ritchie, Perez, Murphy, Joselu
Score prediction: Southampton 0-1 Newcastle United
The game has been selected for Sky Sports TV coverage. You can also follow the match by tuning into BBC Radio Newcastle's live commentary, courtesy of the official NUFC website.