Jurgen Klopp has made a total of seven changes to the side that drew with Aston Villa last weekend, as Kelleher makes his first Premier League start of the season in between the sticks over Alisson Becker.
Milner and Firmino have also been handed starts for their final game in Liverpool shirts, while Joe Gomez, Joel Matip, Kostas Tsimikas and Diogo Jota are also recalled to the first XI.
Mohamed Salah, Trent Alexander-Arnold, Fabinho and Curtis Jones are the only players to hold their places from last weekend, as Ibrahima Konate, Luis Diaz and Cody Gakpo take up spots on the bench.
Meanwhile, outgoing Southampton manager Ruben Selles has made just the one change from last weekend's 3-1 defeat to Brighton & Hove Albion, bringing Kamaldeen Sulemana back in for Joe Aribo in the final third.
Southampton: McCarthy; Bree, Lyanco, Bednarek, Walker-Peters; Lavia, Ward-Prowse; Elyounoussi, Alcaraz, Sulemana; Walcott
Subs: Bazunu, Caleta-Car, Livramento, Doyle, Aribo, S. Armstrong, A. Armstrong, Ballard, Arno-Ameyaw
Liverpool: Kelleher; Alexander-Arnold, Gomez, Matip, Tsimikas; Fabinho, Jones, Milner; Salah, Firmino, Jota
Subs: Adrian, Konate, Henderson, Gakpo, Diaz, Carvalho, Elliott, Arthur, Williams
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