The Saints' fate was sealed in a 2-0 defeat to Fulham last weekend, while Roberto De Zerbi's men were brought crashing back down to earth in a 4-1 midweek humbling against Newcastle United.
Match preview
For the first 45 minutes of Thursday's game at St James' Park, Brighton were completely unrecognisable from the side that trounced title challengers Arsenal at the Emirates last weekend, as Newcastle pressed the life out of De Zerbi's men and got their rewards through Deniz Undav's own goal and a Dan Burn header in the first half.
Undav went from villain to hero early in the second period to spark a frantic finale, but all of the late goalmouth action came in the Brighton box, as strikes from Callum Wilson and Bruno Guimaraes in the dying embers saw the Magpies come out on top against the Seagulls in that avian contest.
An unusually shot-shy Brighton can practically forget about any nights under the bright lights of the Champions League, but the Seagulls remain comfortably entrenched in sixth place in the table, one point better off than Tottenham Hotspur and Aston Villa with a game in hand on both clubs.
Not afraid to tinker with his team selection, De Zerbi's raft of rotations backfired and then some at St James' Park, and Brighton may not even welcome a return to home soil this weekend given their recent Bank Holiday humiliation at the hands of Everton.
However, Brighton have immediately responded to defeat with a win six times in a row in the Premier League - not since October have they suffered back-to-back losses in the top flight - but the more superstitious Seagulls fans should look away now, as there has never been a home win in 11 previous Premier League meetings between Brighton and Southampton.
The images of Southampton's iconic 2014 Premier League team began doing the rounds on social media last week, as a club that birthed the likes of Mauricio Pochettino, Sadio Mane and Toby Alderweireld in English football saw their decade-long stay in the top tier come to an end.
Not even the presence of Rishi Sunak could inspire Ruben Selles's side to deliver a prime performance during Fulham's visit to St Mary's last weekend, as goals from Carlos Vinicius and Aleksandar Mitrovic officially condemned the Saints to Championship football for 2023-24.
Avoiding a last-placed finish is now the sole consolation prize that Southampton can hope for, but even usurping Leicester City into 19th place now seems a stretch - the Foxes are six points clear of the Saints with just two games remaining, not to mention their vastly superior goal difference.
With no pressure weighing heavily on their shoulders, Southampton can at least play with the shackles off in their final two fixtures with Brighton and Liverpool, but they travel to the Amex on a four-game losing streak and without a top-flight win in 11 games since seeing off Leicester at the beginning of March.
Each of the last six Premier League meetings between Brighton and Southampton has seen both teams find the back of the net, and the Saints came away from the Amex with a 2-2 draw last season, but the Seagulls ran out 3-1 winners at St Mary's earlier this term to extend their unbeaten run over their doomed visitors to four matches.
Brighton & Hove Albion Premier League form:
L
W
W
L
W
L
Southampton Premier League form:
L
D
L
L
L
L
Team News
A few egos may have been battered and bruised at St James' Park, but Brighton did not sustain any fresh injury concerns in midweek, which is one minor positive for De Zerbi amid his side's current fitness predicament.
All of Tariq Lamptey (knee), Solly March (thigh), Jeremy Sarmiento (ankle), Adam Lallana (thigh), Jakub Moder (knee) and Adam Webster should sit this one out again, while Joel Veltman's participation is also up in the air due to his own thigh concern. Recently-demoted goalkeeper Robert Sanchez, meanwhile, has been allowed to stay at home for Brighton's last two away days.
After his alterations failed to pay dividends on Tyneside, De Zerbi should recall regulars Alexis Mac Allister, Evan Ferguson and Levi Colwill - who sat out Thursday's loss due to fatigue - as the likes of Jan Paul van Hecke and Danny Welbeck prepare to drop out.
As for Southampton, Selles should also be working with the same group of players who fell short against Fulham, although Che Adams might be able to return to bolster the visitors' attacking ranks.
Romain Perraud (ankle), Armel Bella-Kotchap (thigh), Juan Larios (thigh), Mohammed Salisu (groin) and Valentino Livramento (fitness) make up a quintet of known absentees for the visitors, who should offer minutes to some of their peripheral players with nothing but pride on the line.
Alex McCarthy's time in goal might come to an end as Gavin Bazunu returns, while Kamaldeen Sulemana, Sekou Mara and maybe even the scarcely-seen Mislav Orsic could come into Selles's thinking.
Brighton & Hove Albion possible starting lineup:
Steele; Gross, Dunk, Colwill, Estupinan; Caicedo, Gilmour; Enciso, Mac Allister, Mitoma; Ferguson
Southampton possible starting lineup:
Bazunu; Walker-Peters, Bednarek, Lyanco, Maitland-Niles; Ward-Prowse, Lavia; Sulemana, Alcaraz, S. Armstrong; Mara
We say: Brighton & Hove Albion 3-1 Southampton
Strange things can happen when a side have already been condemned to the drop, and given Brighton's recent shortcomings against bottom-half teams, Southampton should be given free rein to attack a fatigued Seagulls backline this weekend.