Jurgen Klopp's side were held to a dramatic 2-2 draw against Tottenham Hotspur last time out, with Harry Kane scoring the equaliser from the penalty spot with virtually the last kick of the game.
It was another disappointing result for the Reds who have endured a curious January. They become the first team to inflict a Premier League defeat on leaders Manchester City and then lost to struggling Swansea City and were knocked out of the FA Cup by West Bromwich Albion.
Meanwhile, Southampton have been grinding out results since the turn of the year. The Saints have won three and drawn three of seven games in 2018 but are still only two points off the relegation zone.
Here's a look at how you can watch Sunday's clash, along with team news and a match preview.
Date: Sunday, February 11
Time: 4:30 p.m. GMT/11:30 a.m. ET
Venue: St Mary's Stadium, Southampton
TV Info: Sky Sports (UK), NBC (U.S.)
Southampton have few injury problems but will still be without striker Charlie Austin who is yet to return from a hamstring injury picked up in December.
Joe Gomez is a doubt for Liverpool with a knee injury, which means Trent Alexander-Arnold could keep his place in the team, per James Pearce at the Liverpool Echo.
Nathaniel Clyne is still out, although he is closing in on a return to first-team training, per David Lynch for the official Liverpool website.
Adam Lallana is available for the Reds despite being sent off for the Liverpool Under-23s against Tottenham for grabbing George Marsh by the neck, per Jack de Menezes at The Independent.
Sunday's game sees Liverpool defender Virgil van Dijk return to his former team for the first time since his club-record January move to Anfield. The defender is the latest in a long line of players who have swapped Southampton for Liverpool with Clyne, Lallana, Dejan Lovren and Sadio Mane having made the move.
However, Van Dijk has not had the smoothest start to life at his new club and conceded the penalty from which Spurs equalised at Anfield on Sunday. ESPN FC's Alex Shaw sums up the Dutchman's start to life at Liverpool:
The arrival of Van Dijk was never going to solve all of Liverpool's defensive problems, but manager Jurgen Klopp may be concerned at how vulnerable his side remain, despite the huge investment in the centre-back.
However, Liverpool still look irresistible going forward, and Mohamed Salah continued his stunning season with another two goals against Spurs. Football writer Artur Petrosyan showed how Salah is leading the way when it comes to goals and assists in the Premier League:
Liverpool's draw with Spurs means the Reds missed the chance to improve their hopes of a top-four finish as the race for UEFA Champions League places hots up. The Reds head into the weekend in third place, just a point above Chelsea in fourth and two ahead of Spurs in fifth.
While Klopp will be targeting a win, he may also have one eye on Wednesday's Champions League trip to Porto, which may well affect his starting lineup.
That could benefit Southampton who are also fresh from a 3-2 win over West Brom last time out. The victory was their first in 13 top-flight outings, and they showed character to come back from going a goal down when Ahmed Hegazi scored after four minutes.
Centre-back Jack Stephens is the man in form for the Saints, as shown by WhoScored:
There's no doubt Southampton will provide a hostile reception for Van Dijk and Liverpool, but Liverpool have the firepower to cause all sorts of problems, particularly with star man Salah still in top form.