Liverpool's Daniel Sturridge looks to stay hot after scoring 11 goals in his last nine Premier League games, but the Reds will be without Brazilian midfielder Philippe Coutinho.
Brendan Rodgers' side has taken 10 points from its opening four top-flight games of the season to extend its overall unbeaten run to 12 matches after a strong finish to last term.
But this sequence only began after they fell to a 3-1 loss at St Mary's in March, when Morgan Schneiderlin, Rickie Lambert and Jay Rodriguez netted for Mauricio Pochettino's men.
Liverpool's goalscorer on that occasion - Philippe Coutinho - will miss Saturday's encounter with Southampton after suffering a shoulder injury that is expected to keep him out of action for around six weeks in Monday's 2-2 draw at Swansea City.
The Brazilian playmaker has been in fine form in the opening weeks of the campaign, but joins Glen Johnson, Aly Cissokho (both ankle) and Sebastian Coates (knee) on the sidelines.
Wales international midfielder Joe Allen could be in line for a return after his hamstring problem, but Liverpool will once again be without Luis Suarez, who serves the last match of his 10-game suspension.
In the absence of the Uruguay international and Coutinho, Rodgers will continue to rely on Daniel Sturridge for attacking inspiration as the striker looks to continue his red-hot run of goalscoring form.
The former Chelsea man has scored 11 goals in his last nine Premier League outings, including four in four this season despite struggling with a thigh problem.
Southampton goes into the game without a Premier League victory since the opening-day win at West Brom and having failed to score in its last two fixtures against West Ham and Norwich City respectively.
Club-record signing Pablo Daniel Osvaldo is still on the hunt for his first Southampton goal since joining from Roma in August and is likely to lead the line again with Pochettino having a fully-fit squad to choose from.
However, Pochettino’s side has won only one of its last five Premier League away games and just one of its previous eight visits to Anfield - a 2-1 success in December 2003.