Mane had played every minute in the Premier League this season.
Summer signing Ibrahima Konate partners Virgil van Dijk in central defence.
Konate has only started two games for Liverpool until today, with Klopp easing him in slowly following his £36million arrival from RB Leipzig.
Roberto Firmino keeps his place in attack following his recent return to form and is flanked by Diogo Jota and Mohamed Salah.
Salah will look to continue his sensation form, having scored 12 times in 11 games this season including outstanding individual goals against Manchester City and Watford in recent weeks.
Liverpool confirmed XI: Alisson, Alexander-Arnold, Konate, Van Dijk, Robertson, Keita, Henderson, Milner, Salah, Firmino, Jota.
Subs: Adrian, Mane, Gomez, Oxlade-Chamberlain, Jones, Minamino, Tsimikas, Origi, Matip.
Manchester United confirmed XI: De Gea, Wan-Bissaka, Lindelof, Maguire, Shaw, Fred, McTominay, Greenwood, Fernandes, Rashford, Ronaldo.
Subs: Henderson, Bailly, Pogba, Lingard, Dalot, Cavani, Sancho, Matic, Van de Beek.