Jurgen Klopp's side head to St. Mary's Stadium in the late Sunday kick-off to face a struggling Southampton side who sit just two points above the relegation zone.
Liverpool go into the tie after a controversial last-minute penalty prevented them from a much-needed victory against Tottenham, as the race for a top four finish heats up.
Southampton on the other hand, are fighting for Premier League survival. However, they head into this one off the back of a six-game unbeaten run, beating West Brom 3-2 in their last fixture in a thriller at The Hawthorns.
All eyes will be on former Saints man Virgil van Dijk, who will be making his first return to his former club since his long-awaited transfer to Liverpool was finally completed last month for £75m.
Sunday's game could potentially feature four former Saint's players in Liverpool's squad, and with both teams fighting at the opposite ends of the table, a fiery encounter is expected in this one.
Here's everything you need to know about this clash.
Southampton 3-3 Liverpool (August 2000)
A thriller at Southampton's old stomping ground the Den saw Gerard Houllier's Liverpool side throw away a three-goal lead to draw 3-3 come 90 minutes.
Liverpool headed into the break with a comfortable lead. The then 20-year-old Michael Owen found the back of the net twice and the Reds looked set to win the game going into the second-half.
Liverpool captain Sami Hyypia then bagged Liverpool's third with a trademark header, and the game seemed all but sealed for the Merseyside team.
Southampton, however, hit back and two goals from Saint's legend Marian Pahars sealed Liverpool's fate on the day, with Southampton managing to turn the game completely on its head to gain a point.
Virgil van Dijk vs Guido Carrillo
A battle between the two new signings.
Guido Carrillo has yet to open his account for the Saints since being signed for £19m from AS Monaco in last months transfer window. The imposing forward will certainly be looking to use his height to challenge fellow giant and former Saints centre-back Van Dijk in aerial duels, if he gets the nod to start.
However, Despite scoring a last minute winner on his debut, Van Dijk is still trying to find his feet at Anfield and hasn't won a league game for the Reds since his memorable FA Cup derby debut.
Carrillo will certainly be looking to test his recent bad form and prove himself to the Saints fans who will undoubtedly be on Van Dijk's back all game.
Mohamed Salah vs Ryan Bertrand
The Egyptian winger has scored 21 times in the Premier League so far this season as he chases the Premier League Golden Boot award.
This all but means Southampton's Ryan Bertrand will have his work cut out for him when the two collide at St. Mary's.
Bertrand is one of the quicker full-backs in the league and will have to use this to his full advantage against the fellow speedster Salah, if he is to stop the on-fire African Player of the year.
Both teams look set to field fully-fit squads, with no injury concerns on either side.Liverpool expect to welcome back Adam Lallana to first-team duties even after he was sent-off mid-week playing for the Reds U23's side.
Potential Liverpool lineup: Karius. Van Dijk, Lovren, Alexander-Arnold, Robertson, Can, Henderson, Oxlade-Chamberlain, Mane, Salah, Firmino.
Potential Southampton lineup: Forster. Cedric, Stephens, Hoedt, Bertrand, Lemina, Romeu, Ward-Prowse, Tadic, Boufal, Carrillo.
Southampton can't be completely ruled out of this one, however, and the Saints are currently six games unbeaten and showed true grit and determination to get the win last time out against West Brom.
The Saint's can also take inspiration from Swansea's terrific performance against Klopp's attacking outlet, which seemingly halted them completely.
Jurgen Klopp's highly praised front three of Salah, Firmino and Mane will likely be the difference between the two sides in this one. However, Liverpool's inconsistency could always pay dividends for the Saints.