When: Saturday, May 8, 20:15 BST
How to watch: Sky Sports Main Event
Saints have injury concerns
Southampton were flying high at one point this season but head to Anfield in 15th place and still not technically safe.
Of course, it would need something of a miracle from third-bottom Fulham to overhaul the 10-point gap, but Southampton's battling 1-1 draw with Leicester shows they're still focused.
One of the big reasons for Saints' slide down the table has been the drop off in their away form. They've lost five of their last six road trips in the Premier League, tasting defeat at Leeds, Everton, Man City, West Brom and Spurs.
Their only win/non-defeat in that run came at rock-bottom Sheffield United.
What's more, they go in Saturday evening's game without a plethora of regulars. Danny Ings, Ryan Bertrand, Oriol Romeu and Will Smallbone are set to miss out through injury while on-loan Liverpool star Takumi Minamino is ineligible.
Last three meetings:
Southampton 1-0 Liverpool (January 04, 2021)
It was quite an image: Ralph Hasenhuttl sinking to his knees in tears after finally beating one of his managerial heroes.
A Danny Ings goal after just two minutes settled the contest and Liverpool's response was tepid. Indeed, they didn't manage a shot on target until the 75th minute - their latest in a Premier League match for five years.
Jurgen Klopp's men actually finished the match still top of the table, but it was a sign of things to come.
Liverpool 4-0 Southampton (February 01, 2021)
Liverpool also finished this game on top of the table but this time their lead was a staggering 22 points after making it 24 wins and a draw from their opening 25 games.
A 20th straight home victory was secured with four second-half goals after the visitors had kept the hosts at bay during the opening 45.
Former Southampton star Alex Oxlade-Chamberlain fired in the first before skipper Jordan Henderson doubled the lead on the hour mark. Mo Salah scored twice in the final 20 minutes to wrap up another routine win.
Southampton 1-2 Liverpool (August 17, 2019)
This was just the second game of Liverpool's dominant 2019/20 title season and it looked to be a straightforward victory until a late wobble.
That should have been that but stand-in goalkeeper Adrian's clearance rebounded into the net off Danny Ings' shin after 83 and the former Reds striker had a golden chance to level late on.
Head-to-head - last 10 meetings
Liverpool wins: 6
Southampton wins: 3
Liverpool scored: 17
Southampton scored: 5
Liverpool hopes of top four starting to disappear
Another capitulation by Leicester hasn't emerged; Chelsea are finishing the season on a high; West Ham just aren't going away.
In short, Liverpool's chances of a top four finish are fading. They're now 2/1 to land a Champions League slot which equates to a 66% chance that they won't.
One added problem is that their bid to gain momentum was halted by the cancellation of last weekend's game against Manchester United. That allowed Leicester to move nine clear of the Reds, while Chelsea pulled seven in front. West Ham have a four-point advantage although Liverpool have a game in hand on all three.
A possible positive spin is that the rearranged game at Old Trafford comes just two days after United play Lecester, so the hosts could be jaded.
After the Southampton and Manchester United games, Liverpool's run-in is West Brom (a), Burnley (a) and Crystal Palace (h).
Hope therefore still remains, but it's out of Liverpool's hands for now.
Liverpool's last five results:
Arsenal 0-3 Liverpool (Jota 2, Salah)
Liverpool 2-1 Aston Villa (Salah, Alexander-Arnold)
Liverpool 0-0 Real Madrid
Leeds 1-1 Liverpool (Mane)
Liverpool 1-1 Newcastle (Salah)
Scoreline prediction: Liverpool 3-0 Southampton
After the visit to Merseyside, Southampton have home games against Crystal Palace, Fulham and Leeds: in other words, some good opportunities to confirm survival and climb towards mid-table.
That makes this game something of a free hit but Saints haven't exactly impressed in away matches against the big teams recently, their defeats including a 9-0 hammering at Manchester United and a 5-2 loss at Manchester City.
Liverpool were horrible at home for a while but they've created more chances in recent Anfield outings and, at some point, some of those will start flying in.
Southampton have lost 4-0, 3-0 and 3-0 on their last three trips to Liverpool and, with the champions having far fresher legs after the United game was cancelled, another 3-0 is worth a punt at 17/2 with bet365.
Best Goalscorer bets
Mo Salah has scored five times in those above three Liverpool home wins over Southampton.
Twice he's scored a brace and the Egyptian superstar is 16/5 to bag two or more.
Salah (20 goals) is one behind Harry Kane in the race for the Golden Boot and it's a prize he values highly.
He'll be shooting at every opportunity, is on penalty duties of course, and it's just a case of how many he can stick away.
I'll back Salah to score two or more but also take a punt on him scoring his second home hat-trick of the campaign. That's a 14/1 shout with William Hill.