Jurgen Klopp's side beat Norwich City in their 2019-20 opener last Friday before overcoming Chelsea on penalties in the UEFA Super Cup on Wednesday. Southampton, meanwhile, suffered a 3-0 defeat at Burnley in their league opener last time out.
A strong pre-season would have left Southampton feeling fairly confident ahead of their trip to Burnley. It was a poor start from the Saints, though, with Sean Dyche's side scoring three times without reply to pick up all three points on the opening weekend of the 2019-20 campaign.
Southampton were actually in the game for long spells, but three goals in the space of 12 second-half minutes made it a comfortable conclusion for the Clarets. Suffering an opening-day defeat was far from ideal, and a home game against the European champions is not quite what the fans would have wanted at this point.
The fact that Liverpool had to play a demanding 120 minutes of football on Wednesday night means that Southampton might be in with more of a chance. However, the Saints have lost each of their last four Premier League games with the Merseyside giants - including a 3-1 defeat at St Mary's as recently as April.
Between 2013 and 2017, Southampton claimed eighth, seventh, sixth and eighth in the top flight. The team only finished five points clear of the bottom three last season, though, and also only just survived relegation in 2017-18, which is an indication of their troubles in recent years.
It was a relatively quiet summer for the club in terms of transfers - Danny Ings's loan move from Liverpool was made permanent, though, while Che Adams and Moussa Djenepo also arrived. Ings and Adams both featured in the defeat to Burnley but Djenepo was an unused substitute.
Ralph Hasenhuttl appears to be keen to use a 3-4-3 formation this season, with Ings, Adams and Nathan Redmond operating as the front three. That will place a lot of pressure on the likes of Oriol Romeu and James Ward-Prowse in midfield, though, and the pair were overrun in the second half against Burnley last time out.
The fact that Southampton only won nine Premier League matches last season is a concern, especially when considering that Cardiff City were relegated having won 10. A record of 12 draws ultimately proved enough to keep the Saints in the division, although they might have to suffer again this term.
It is not as if Southampton have time to settle into the new campaign with a kind fixture list, though, as they face a difficult trip to Brighton & Hove Albion in their next league game before hosting a seemingly resurgent Manchester United before the end of the month.
Recent form: L
Liverpool opened their 2019-20 Premier League challenge with a comfortable 4-1 win over Norwich on August 9. The Canaries actually played quite well for long periods of the game; four first-half goals ultimately saw the Reds triumph, though, as they made the perfect start to the new season.
There is no question that Klopp will be targeting another win this weekend. However, 120 minutes of demanding football in Istanbul on Wednesday night could prove to be an issue. The Merseyside giants did beat Chelsea on penalties following a 2-2 draw but it was a tough game in difficult conditions.
In truth, neither Klopp nor Frank Lampard would have wanted extra time, and both would surely have been content with the game going straight to penalties. That was not the case, although it did end well for the Champions League holders as they added more silverware to their cabinet.
A Sunday afternoon or Monday night match would have been preferable for Liverpool. That luxury has not been afforded, however, and they will start their game at 3pm on Saturday. St Mary's has been a happy hunting ground in recent years, though, and last year's runners-up will be eyeing another win this weekend.
Liverpool have a huge game at home to Arsenal next weekend - a trip to Burnley will then follow ahead of the September international break. Klopp's side will then host Newcastle United before travelling to Chelsea towards the end of next month, which will also see the Champions League group stages begin.
A quiet summer in terms of recruitment means that Liverpool do not have much room for manoeuvre when it comes to injuries. Number one goalkeeper Alisson Becker has already been lost for a few weeks, while Naby Keita missed the Chelsea game with a muscular problem as his injury issues continued.
It would be fair to say that the Reds were fortunate last season when it comes to injuries. If the likes of Sadio Mane, Roberto Firmino, Mohamed Salah and Virgil van Dijk can avoid setbacks then it should be another successful campaign for the club but nothing is guaranteed.
Southampton will have also been encouraged by the fact that Norwich and Chelsea have both had joy against Liverpool this season. The former should have scored more than once at Anfield last week while the latter created a whole host of chances in addition to scoring twice in Istanbul.
Recent form: W
Recent form (all competitions): WW
Southampton have no fresh injury concerns from the defeat to Burnley, although defender Sam McQueen remains a long-term absentee with a serious knee injury.
It seems likely that Hasenhuttl will make changes from the loss against the Clarets, with an extra midfielder potentially being brought into the side at the expense of a forward.
There is every chance that Pierre-Emile Hojbjerg could come into the XI for Adams, with Ward-Prowse moving slightly forward to supplement Redmond and Ings in the final third.
As mentioned, Alisson will once again be absent for Liverpool, meaning that former West Ham United stopper Adrian will start between the sticks once again.
Nathaniel Clyne is the team's only other confirmed absentee, although it seems unlikely that Keita will be involved after sitting out the clash with Chelsea with a muscular problem.
Trent Alexander-Arnold, Firmino and Georginio Wijnaldum should all return to the XI having been named on the bench against Chelsea, while Mane is expected to start after coming through the UEFA Super Cup unscathed.
Southampton possible starting lineup:
Gunn; Bednarek, Yoshida, Vestergaard; Valery, Romeu, Hojbjerg, Bertrand; Ward-Prowse, Redmond; Ings
Liverpool possible starting lineup:
Alisson; Alexander-Arnold, Gomez, Van Dijk, Robertson; Henderson, Fabinho, Wijnaldum; Mane, Firmino, Salah
Head To Head
Liverpool lead the head-to-head 55 wins to Southampton's 30, with the remaining 25 games ending level.
As mentioned, the Merseyside giants have been victorious in each of the last four Premier League games between the two teams - including a 3-1 success at St Mary's in April.
That said, Southampton recorded a 3-2 win over the Reds on home soil in March 2016, while the Saints went unbeaten in five games against the Merseyside giants between the start of 2016 and middle of 2017.
We say: Southampton 1-3 Liverpool
Fatigue could well play a role in this game after Liverpool's involvement in the UEFA Super Cup. Despite tipping Southampton to find the back of the net, we are finding it difficult to back against Klopp's side due to the quality they can call upon all over the field. We fancy a fairly comfortable 3-1 away win.
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