The 14:00 GMT kick-off presents a tough test for the Reds against Ralph Hasenhuttl's in-form Saints but confidence will be high after the wins over West Brom and Istanbul Basaksehir, following the international break.
The boss has handed Donny van de Beek a first league start but Anthony Martial is not in the squad.
Mason Greenwood is back in the line-up, after an impressive cameo against Basaksehir, and the other change to that Champions League win in midweek is the inclusion of Nemanja Matic to bolster the midfield.
Martial and Edinson Cavani, who is on the bench, make way.