Liverpool face their third home game in a week, having followed last Saturday's 4-0 dismantling of Arsenal with a 2-0 win over Porto in the Champions League.
There is a slight complication in having to turn around from a Wednesday Champions League match to a Saturday fixture in the Premier League for only the second time this season, but the first ended well with a 3-0 home win over Crystal Palace.
Jurgen Klopp's side sit third in the table on 25 points, four behind Chelsea and one behind Manchester City, and it is vital for them to keep pace with their title rivals in this pre-Christmas period.
Klopp has been hampered by a lengthy injury list recently, but James Milner, Andy Robertson and Divock Origi all returned as second-half substitutes against Porto.
Naby Keita is getting closer to a return but Curtis Jones, Joe Gomez, Roberto Firmino and Harvey Elliott are still out.
Saints' run halted
Southampton's mini good run of three wins and a draw came to a halt last Saturday with a 2-1 defeat at Norwich, who were bottom of the table before the match.
Before that Ralph Hasenhuttl's side had beaten three middling teams in Leeds, Watford and Aston Villa (all 1-0) and drawn with 18th-placed Burnley (2-2 home).
The Saints start this match in 13th place with 14 points, five clear of the relegation zone.
Nathan Redmond looks set to return after missing the Norwich match following the birth of his daughter and so could Moussa Djenepo, who was absent for personal reasons.
Liverpool were virtually unstoppable at Anfield a few seasons back but they are not quite as assured now, although many will see them as a banker at 1.321/3.
In 2018/19, when they amassed 99 points and ran Manchester City so close for the title, their home record was W17 D2 L0 and in their following championship-winning campaign it was W18 D1 L0.
Last season the home win rate dropped to 53% and it is 50% so far this season with a record of W3 D3 L0, although it is probable that underestimates them as they have already faced title rivals Chelsea (1-1) and City (2-2) at Anfield.
This season's other home draw was against ninth-placed Brighton (2-2), which was disappointing after throwing away a two-goal lead but not dreadful considering Brighton's good start to the season.
Since then Liverpool have won three consecutive home games to nil, 4-0 against Arsenal sandwiched between 2-0 Champions League wins over Atletico Madrid and Porto.
Their other two Premier League wins have also been to nil - 2-0 against Burnley and 3-0 against Crystal Palace - and that option looks well priced at 2.3211/8.
Southampton have lost to nil on their last four trips to Anfield (3-0 twice, 4-0 and 2-0 last season).
Hasenhuttl's side have a W1 D2 L3 away record this season, although like Liverpool that is affected by having already played City (0-0) and Chelsea (3-1).
The win came at Watford (1-0) and the other draw was against bottom club Newcastle (2-2), so it looks as if they will need a rearguard action like they had against City to get anything here.
The Saints have lost 13 of their last 14 away games when conceding, the draw against Newcastle being the exception, and a clean sheet is likely to be their prime objective.
That looked difficult against City and they achieved it, but it is possibly even more difficult at Anfield. Since the start of 2018/19 Liverpool have had only seven blanks in 63 home matches and most of those came in a tricky spell at the start of this year when they were missing Virgil van Dijk badly.
Since Van Dijk signed from Southampton in the 2018 January transfer window, he has become the rock on which Liverpool's success has been built.
Their home record with the Dutchman in the side is W54 D8 L0, which emphasises the scale of the task facing the Saints.
Liverpool top the table for matches with over 2.5 goals, having had 10 out of 12 (83%) above that mark, including the last nine in a row. It is no surprise to see over 2.5 goals is very short at 1.454/9.
Much of that is down to their own scoring power. Klopp's side are the Premier League's top scorers (35 at a rate of 2.92 per game) and have scored three goals or more in seven out of 12. Liverpool are 1.9620/21 to go over 2.5 goals.
Southampton are at the other end of the scale. The goals average of their matches is the second lowest in the Premier League at 2.08 and 58% of their games have had under 2.5 goals.
On current form Liverpool are capable of another high score but Southampton's goalless draw at City is a warning to anyone who thinks it will be easy.
Southampton have lost 13 of their 17 Premier League away games in 2021 (W2 D2), conceding 43 goals in this run (2.5 per game). Indeed, Saints have lost more games and conceded more goals away from home than any other Premier League side in this calendar year so far. A Liverpool win with over 2.5 goals is available at 1.715/7.