Liverpool's title challenge takes them to St Mary's on Friday night as they look to ensure top spot with just five games of their season remaining.
Sunday's dramatic 2-1 win over Tottenham Hotspur saw Jurgen Klopp's side move back two points clear at the summit, but Manchester City could leapfrog them again with victory over Cardiff City on Wednesday night.
The champions are in FA Cup action this weekend, though, meaning that beating Southampton on Friday will leave Liverpool top for a longer period of time - even if the fate of the trophy still lies in Man City's hands.
Here, Sports Mole looks at how Liverpool could line up for another must-win contest.
Out: Alex Oxlade-Chamberlain (hamstring)
Doubtful: Virgil van Dijk (ankle), Joe Gomez (ankle)
> Click here for Liverpool's latest injury and suspension news ahead of this match
Concerns over the fitness of Virgil van Dijk threatened to overshadow the euphoria of the Spurs victory, but the Liverpool talisman is already training as normal and will feature against his former club on Friday night.
Other Saints alumni such as Dejan Lovren and Adam Lallana may have to settle for a place on the bench once again, but Sadio Mane does look certain to return to his old stomping ground too.
Joe Gomez could be involved in some capacity as he nears his return from a lengthy ankle injury, although Klopp is unlikely to throw him straight back into the starting XI after such a long time out.
The clamour for Fabinho to be handed more starts is growing amongst Liverpool fans and Klopp is expected to oblige for this match, while Naby Keita could also come in with Jordan Henderson and James Milner perhaps being held back for the Champions League tie with Porto next Tuesday.
Mohamed Salah will continue his search for his 50th Premier League goal for Liverpool, meanwhile, having now gone almost two months without finding the back of the net in any competition.
