At the opposite end of the Premier League table, third-placed Newcastle have all but secured Champions League football as they sit eight points inside the top four.
Match preview
After claiming a memorable 6-1 victory over Tottenham Hotspur last weekend, Newcastle made light work of Everton on Thursday, with Callum Wilson bagging a brace at Goodison Park to pile more pressure on the relegation-threatened Toffees.
Joelinton and Jacob Murphy also scored for the second game running in the 4-1 win, while in-form forward Alexander Isak - who has netted seven goals in his last eight league outings - came off the bench to produce an eye-catching cameo.
Thanks to a couple of victories in the space of five days, the Magpies have now won seven of their last eight Premier League encounters, solidifying their place in the top four with six games remaining.
When you look at the bigger picture, Eddie Howe's side have lost just four of their 32 Premier League matches this season, meaning that no team has suffered fewer defeats than Newcastle in 2022-23.
The Magpies also boast the best defensive record in England's top tier, having conceded 26 goals this term, although they have only managed to keep two clean sheets in their previous 12 Premier League outings.
Southampton's slide towards the Championship continued as Bournemouth claimed a 1-0 victory at St. Mary's on Thursday, with substitute Che Adams seeing his 90th-minute equaliser ruled out for offside.
The Saints showed great spirit to snatch a point at the Emirates Stadium prior to Thursday's defeat, playing out a thrilling 3-3 draw with Arsenal, although the visitors led 2-0 and 3-1 before the Gunners mounted a late comeback.
In addition to losing four of their last five matches, Southampton have failed to win any of their previous eight, taking only three points from a possible 24 since defeating Leicester City in early March.
As a result, Ruben Selles's men find themselves four points shy of 19th-placed Everton and six points from safety with five matches left, so they will need to perform a minor miracle if they want to avoid relegation.
Having managed to win just three of their last 22 Premier League games - suffering 15 defeats in the process - Southampton look destined to struggle in front of an expectant and intimidating Toon Army.
Newcastle United Premier League form:
W
W
W
L
W
W
Southampton Premier League form:
D
L
L
L
D
L
Team News
Eddie Howe made several changes in midweek, with Dan Burn, Jacob Murphy and Alexander Isak making way for Matt Targett, Miguel Almiron and Callum Wilson.
Those changes could be reversed on Sunday as Howe attempts to limit fatigue during a tight fixture schedule, although Bruno Guimaraes, Joe Willock and Sean Longstaff are expected to remain in midfield.
Sven Botman, Fabian Schar and Kieran Tripper will continue in the backline, while Allan Saint-Maximin and Emil Krafth remain sidelined through injury.
Southampton look set to be without the injured trio of Mohamed Salisu, Romain Perraud and Juan Larios this weekend, while Tino Livramento and Armel Bella-Kotchap are doubts for Sunday.
There are also question marks over the availability of James Ward-Prowse after the club captain was substituted at half time in Thursday's defeat to Bournemouth due to illness.
Carlos Alcaraz will continue in an advanced role alongside Theo Walcott, with Romeo Lavia and Mohamed Elyounoussi operating behind the forward line.
Newcastle United possible starting lineup:
Pope; Trippier, Schar, Botman, Burn; Longstaff, Guimaraes, Willock; Murphy, Isak, Joelinton
Southampton possible starting lineup:
McCarthy; Walker-Peters, Bednarek, Caleta-Car, Perraud; Elyounoussi, Ward-Prowse, Lavia, Armstrong, Walcott, Alcaraz
We say: Newcastle United 4-0 Southampton
Having netted 10 goals across recent wins over Tottenham and Everton, in-form Newcastle look set to notch another high-scoring victory against struggling Southampton, who are on course to suffer a sixth defeat in eight matches.