The Brazilian overcame his injury during the international break, while the Senegal speedster felt a recurrence of the problem after helping secure his country’s World Cup spot at the expense of South Africa.
Mane returned to Melwood during the FIFA interval to continue his recovery and runs out from the off against his former club.
Jordan Henderson is also part of the XI having recovered from a thigh complaint, but the encounter comes too soon for ex-Saints star Adam Lallana.
The England international, who had a more serious version of the captain’s injury, is waiting to make his first appearance of the season having resumed full training on Wednesday.
Joel Matip - also nursing a thigh issue - misses out with Dejan Lovren starting for Liverpool for the first time since his torrid showing in last month's defeat at Tottenham.
Liverpool starting XI: Mignolet, Alexander-Arnold, Klavan, Lovren, Moreno, Henderson, Wijnaldum, Coutinho, Salah, Mane, Firmino.
Liverpool subs: Karius, Gomez, Milner, Can, Oxlade-Chamberlain, Sturridge, Solanke.
Southampton starting XI: Forster; Cedric, Van Dijk, Hoedt, Bertrand; Romeu, Davis; Tadic, Boufal, Redmond; Long.
Southampton subs: McCarthy, Yoshida, Hojberg, Ward-Prowse, Targett, Gabbiadini, Austin.