The final positions of both teams have already been confirmed, with Liverpool guaranteed to finish in fifth place and Southampton condemned to rock-bottom following a dismal campaign.
Match preview
Both of these clubs will be keen to consign the 2022-23 campaign to history as quickly as possible, with Liverpool and Southampton having suffered hugely underwhelming seasons to varying degrees.
For Liverpool, the damage was done in the first two-thirds of the season, although they will take some positivity into the summer having seemingly turned the corner with an ongoing 10-match unbeaten streak.
That included a seven-game winning run which came to an end at Anfield against Aston Villa last time out - a result which left their already-slim Champions League hopes hanging by a thread.
Manchester United then delivered the final blow by cruising past Chelsea on Thursday night to put the top four beyond reach, leaving Liverpool to play Europa League football next term as a result of their lowest finish in any of Jurgen Klopp's seven full seasons in charge.
Klopp was keen to stress that fifth is still a good result considering where they sat just a couple of months ago, but there is no doubt that a rebuild is required at Anfield in the transfer market this summer, particularly in midfield.
Before that, a Liverpool side more used to battling for the Premier League title on the final day in recent years will look to end a disappointing campaign on a high despite nothing tangible depending on the match.
The Reds have won three Premier League away games on the trot to suggest that their travel sickness is now behind them, having only won three of their first 15 on the road this season, losing eight of those. Indeed, should Liverpool win on Sunday then almost half of their away points for the entire campaign would have come in their final four such games.
Klopp's side have also scored 11 goals in those three successive wins - as many as they had in their previous 13 away games - and they will be confident of bolstering that tally further against a team that has already shipped 69 goals this season.
Indeed, Liverpool could hardly have hand-picked a better final-day opponent having won 10 of the last 11 league meetings against Southampton, and conceding only five goals in their last 13.
Liverpool have also won each of their last six games on the final day of a season, stretching back to 2015-16, whereas Southampton have lost their last two and now find themselves in very real danger of suffering three such defeats in a row for the first time since a run of seven which ended in 1939.
Even more worryingly for the hosts, the team that finished bottom of the Premier League has only won on the final day once in the last 20 seasons, and that is a position they cannot improve even if they pull off a shock against the Merseysiders on Sunday.
It has been a miserable season for the Saints which has seen them go through three managers, win a league-low six games and lose a league-high 25, while only Wolverhampton Wanderers have scored fewer goals.
The club has already confirmed that current boss Ruben Selles will leave at the end of the campaign, having failed to build on an encouraging 1-0 win over Chelsea at Stamford Bridge in his first match at the helm.
That proved to be one of only two wins he has enjoyed to date, and their relegation was confirmed with a whimper having gone 12 games without a win - the third-longest streak in their league history - and lost each of their last five outings ahead of Liverpool's visit.
One possible straw they can clutch at ahead of this weekend is that the three points they have taken from the last 36 on offer have curiously come against Manchester United, Tottenham Hotspur and Arsenal, so there is some form for raising their game against the bigger teams in the division.
However, even a win on Sunday would do nothing to mask what has been a disastrous season for the club, and all eyes will already be on how they can immediately bounce back from their first season in the second tier since 2011-12 under expected incoming boss Russell Martin.
Southampton Premier League form:
D
L
L
L
L
L
Liverpool Premier League form:
W
W
W
W
W
D
Team News
With neither side having anything to fight for, both managers may look to use the opportunity to bid farewell to some departing players.
The most notable confirmed departee is Roberto Firmino, who scored on his Anfield adieu last weekend and was fittingly serenaded by the home fans, but who will surely be handed a 362nd and final appearance of a glittering Liverpool career at St Mary's.
Naby Keita will miss out on his own farewell on the pitch due to injury, but there could be roles for out-of-contract duo Alex Oxlade-Chamberlain and James Milner, the latter of whom would be making a record-equalling 16th Premier League final-day appearance if he does feature.
In terms of absentees, Klopp confirmed in his pre-match press conference that Ibrahima Konate (illness) and Andrew Robertson (groin) are both doubts for the game, while Thiago Alcantara, Stefan Bajcetic and Calvin Ramsay remain sidelined.
Darwin Nunez is back in full training, though, and should be available for the visitors.
Mohamed Salah, who wasted no time in publicly expressing his disappointment at missing out on Champions League football, will look to continue his blistering form in recent months, having been directly involved in more goals than any other Premier League player since the beginning of March, scoring 11 and creating six.
For the hosts, the match could be most significant for being the final time the home crowd see James Ward-Prowse in a Southampton shirt, with the England international widely expected to end his 20-year association with the club this summer following their relegation.
The club captain has been an ever-present in the league this term and will make his 409th appearance for the Saints in midfield - likely one of a number of players who will bid farewell to the home fans this weekend.
Mohamed Elyounoussi, Theo Walcott and Willy Caballero are all out of contract at the end of the campaign, while the likes of Romeo Lavia, Kyle Walker-Peters and Che Adams have been linked with exits.
Adams will not feature on Sunday due to a calf injury, while Selles also revealed in his pre-match press conference that Mohammed Salisu, Juan Larios and Armel Bella-Kotchap are also sidelined for the game, and that Paul Onuachu is a doubt due to a back issue.
Romain Perraud remains a long-term absentee, but Tino Livramento will be handed a cameo at the end of the game after featuring for 20 minutes against Brighton & Hove Albion last weekend - his first appearance for 392 days following a serious injury.
Southampton possible starting lineup:
McCarthy; Bree, Bednarek, Lyanco, Walker-Peters; Ward-Prowse, Lavia; Walcott, Alcaraz, Elyounoussi; Aribo
Liverpool possible starting lineup:
Alisson; Alexander-Arnold, Matip, Van Dijk, Tsimikas; Milner, Fabinho, Oxlade-Chamberlain; Salah, Firmino, Diaz
We say: Southampton 0-2 Liverpool
Final-day dead-rubbers are always difficult ones to call, but it is impossible to back Southampton in this match given their form over the last couple of months.
At home in particular they have been dreadful, winning the fewest games and scoring the joint-fewest goals, while also losing the most games and conceding the joint-most, so there is little reason to suggest that they might give the St Mary's supporters something to shout about on the final day.