The Saints are currently sat in second place in the Premier League table as City languish nine points behind leaders Chelsea.
The key to Southampton's success this season has been the consistency in Ronald Koeman's team selections and that remains the case again this afternoon.
Dusan Tadic starts behind Graziano Pelle and Sadio Mane while Fraser Forster remains in goal.
The champions, on the other hand, see Pablo Zabaleta, Fernandinho, Yaya Toure and Stevan Jovetic all return after missing out on the starting line up during the Champions League win over Bayern Munich.
Southampton: Forster, Clyne, Fonte, Alderweireld, Bertrand, Wanyama, Schneiderlin, Tadic, Davis, Mane, Pelle.
Man City: Hart, Zabaleta, Kompany, Mangala, Clichy, Fernandinho, Toure, Navas, Jovetic, Nasri, Aguero.Reuse content