Lallana suffered a minor injury during the international break, with a scan on Thursday ruling him out of contention at St. Mary’s.
However, Philippe Coutinho has recovered from a similar problem, and has been passed fit to start.
Including Coutinho, Klopp has called upon a strong Liverpool lineup to take on the struggling Saints, who head into the clash 10th in the Premier League table, having taken 13 points from 11 games.
This will be the first time Can and Wijnaldum start together in a competitive clash, following Lallana’s injury.
Mane is making his first outing at St. Mary’s since leaving for Merseyside in a £30 million deal in the summer, and having scored six goals in 10 league games so far this season, will be looking to continue his fine form.
Southampton: Forster; Cedric, Fonte, Van Dijk, Bertrand; Romeu, Davis, Hojbjerg; Redmond, Boufal, Austin
Substitutes: Taylor, Yoshida, Martina, Clasie, Reed, Long, Rodriguez
Liverpool: Karius; Clyne, Matip, Lovren, Milner; Henderson, Wijnaldum, Can; Mane, Coutinho, Firmino
Substitutes: Mignolet, Lucas, Klavan, Moreno, Grujic, Sturridge, Origi