Saints head to Anfield having won once in their last five top-flight fixtures.
That victory came against Ipswich Town on their travels in early February, securing a 2-1 win at Portman Road.
Overall, Southampton have faced a difficult campaign following promotion from the Championship last summer, sitting bottom of the table after 27 games.
They have gathered nine points in total and are 13 adrift from safety in the division.
James Bree has been ruled out of the trip to Merseyside.
But the visitors have defender Jan Bednarek and former Liverpool midfielder Adam Lallana available again after injury.
Kyle Walker-Peters has shaken off the knock picked up in their last outing at Chelsea on February 25.
The Reds and Southampton have faced off twice already in this campaign, with both meetings coming at St Mary's.
Arne Slot's men claimed a 3-2 victory in the league in November, with a late Mohamed Salah penalty sealing three points after an earlier finish that followed Dominik Szoboszlai's opener.
They also travelled to the south coast in the Carabao Cup just before Christmas, earning another hard-fought win.
Darwin Nunez and Harvey Elliott were both on target for the visitors, who advanced to the semi-finals with a 2-1 scoreline.
Southampton manager Ivan Juric
"Before the match, I'm always optimistic and then after maybe I think differently. But before the match I always see the possibility of doing something good.
"If you do some things, they [Liverpool] will find another way to beat you. If you are [in a] low block, they will find a way to beat you. I think we have to be perfect in both things – sometimes press, sometimes low block. We will see. We have to play well."
