Mane was a doubt after tweaking a hamstring problem while on international duty, but the Senegal attacker has been passed fit to start at Anfield.
Captain Jordan Henderson has returned to the first XI after missing the Reds' 4-1 victory over West Ham United a fortnight ago, while Philippe Coutinho is also back following a spell on the sidelines.
Virgil van Dijk, who was heavily linked with a move to Anfield in the summer, starts at the back for the Saints.
Liverpool: Mignolet; Alexander-Arnold, Lovren, Klavan, Moreno; Henderson, Wijnaldum, Coutinho; Mane, Salah, Firmino
Subs: Karius, Milner, Oxlade-Chamberlain, Gomez, Sturridge, Solanke, Can
Southampton: Forster; Cedric, Van Dijk, Hoedt, Bertrand; Romeu, Davis; Tadic, Boufal, Redmond; Long
Subs: McCarthy, Yoshida, Hojbjerg, Ward-Prowse, Targett, Gabbiadini, Austin
Follow Sports Mole's live text commentary of the match here.