Brendan Rodgers' men were beaten 1-0 in the reverse fixture in September thanks to Dejan Lovren's second-half strike - their only reverse at Anfield this term.
The fourth-placed Merseysiders will look to turn the tables on Southampton on Saturday, and they head to St Mary's riding the crest of a wave in the Premier League.
Liverpool are the English top-flight's form team, and sit just four points behind leaders Chelsea having won six and drawn two of their last eight games.
That run includes three successive victories, with their most recent triumph coming in the thrilling 4-3 home win over Swansea City last weekend courtesy of a brace apiece from Daniel Sturridge and Jordan Henderson.
And with Manchester City not in Premier League action this weekend due to the League Cup final, Liverpool can move up to third - or even second if Arsenal lose at Stoke City - by extending their winning run on the south coast.
Defender Mamadou Sakho may be in line for a return for the visitors after recovering from a hamstring injury sustained in the 2-1 defeat at Chelsea in December, while Rodgers has been handed a further boost with the news that Lucas Leiva is back in training after a knee problem.
Saturday's match will come too soon for the Brazil international, however, while full-back Jose Enrique remains sidelined with a long-standing knee injury of his own.
St Mary's has been something of a bogey ground for Liverpool, with Southampton winning four of the previous five Premier League encounters there, including the last three.
Southampton coach Mauricio Pochettino will be keen for his side - who saw a six-game unbeaten league run end at West Ham last time out - to exploit Liverpool's shaky defence, with only four teams having kept fewer clean sheets than the title contenders this term.
Pochettino's men are also just one of two sides to keep a clean sheet against Liverpool's wealth of attacking talent this season, with the other being Arsenal.
However, the Argentinian - for whom Jos Hooiveld remains a doubt with an eye injury - will be wary of the Premier League's in-form striker Sturridge, who has netted in eight consecutive matches to help establish Liverpool as the division's top scorers with 70 goals in 27 games.
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.