The striker Mark McGhee tried to sign last season broke depleted Albion's hearts.
Two goals by Dexter Blackstock, the second with four minutes left, earned Southampton their first points under George Burley and deprived the Seagulls of a bonus point in their battle to beat the drop.
McGhee wanted to borrow Blackstock last season but the 19-year-old, unimpressed by Withdean, opted for Plymouth instead.
Albion managed to keep Blackstock quiet during a loan stint with Derby when they drew 0-0 at Withdean in November.
He still impressed that day playing alone up front and his decisive double in an entertaining South Coast derby followed the goal he scored in new boss Burley's third defeat in a row at Cardiff on Saturday.
It was a frustrating finish to an afternoon rich in hope for Albion, missing ten players through injury, suspension and illness.
Two more, Leon Knight and Michel Kuipers, were left out of the team. There was already a big question mark over Knight's future at the club after his recent differences with the manager and Kuipers' animated discussion on the pitch with McGhee before the match suggested the Dutchman was not best pleased to be replaced by Florent Chaigneau.
McGhee blamed himself for making too many changes to a winning team at Luton last week. His selection was vindicated yesterday by the performances of those he brought in.
Along with Chaigneau's first Championship start for the club, the absences of banned trio Paul Reid, Dean Hammond and Colin Kazim-Richards were covered by a debut for 18-year-old Joel Lynch at leftback, a switch to central midfield for the recalled Kerry Mayo and a return up front for Jake Robinson.
Chaigneau, kicking well, recovered from an unconvincing first half to make a series of saves after the break.
Lynch, an unused substitute for the home game against Sheffield United last season, performed with considerable promise, while the energetic Mayo struck Albion's well-crafted equaliser with his weaker right foot after Robinson showed great awareness in setting him up.
Although Southampton came into the game out-of-form and crippled by injuries themselves, they were still entitled to have too much quality for the Seagulls.
A bench including the Premiership experience of David Prutton and Brett Ormerod, plus highly-rated whizz-kid Theo Walcott, emphasised the differences between the squads in terms of strength in depth.
Among the three rookies in reserve for Albion were free-scoring prospect Joe Gatting, who made his debut in stoppage time at the expense of a below-par Seb Carole.
All things considered, McGhee's makeshift line-up did well to run Saints so close, although that will be of little consolation when he looks at the League table today.
Bereft of funds to strengthen during the January transfer window, it is a bad time for Albion to have dropped back into the relegation zone with tough Championship assignments ahead at home to Leeds and away to Sheffield United following Coventry's FA Cup visit.
At least McGhee will have more players to choose from on Saturday and he must be heartened by the way his patched up side responded to an early deficit yesterday.
A sweeping move from the back by Southampton in the tenth minute, launched by an exchange between Martin Cranie and Djamel Belmadi, ripped through Albion's right side and Blackstock latched onto Cranie's pass to slot past Chaigneau from deep inside the box.
The widely predicted script was confounded when Mayo levelled 11 minutes later. A determined run and then cross to the near post by Alex Frutos was controlled by Robinson.
He tried to turn and get in a shot himself but, realising Mayo was better placed, laid the ball back for the long-serving stalwart to beat the unsighted Antti Niemi with a low drive from ten yards.
Mayo now holds the distinction of scoring Albion's first goals of both 2005 and 2006, his previous strike coming a year ago today against Watford at Withdean.
Belmadi must still be wondering how he failed to join Mayo and Blackstock on the scoresheet.
In the first half the Algerian midfielder, one of six changes to the Southampton side beaten at Cardiff, had a long range effort fumbled by Chaigneau, then left the giant Frenchman groping thin air with the sweetest of shots from 20 yards which hit the angle of post and crossbar.
In the second half two more attempts from Belmadi, the second a dipping 25-yarder, were pushed over by Chaigneau.
The latter spectacular stop by the giant loanee from Rennes, six minutes from time, looked like preserving another useful away point, particularly after substitute Ormerod had squandered a glorious opening on the hour by blazing over from the edge of the six-yard box.
Frutos showed Belmadi was not the only player capable of unleashing from distance just after that with a ferocious effort from 25 yards which Niemi parried but Albion's spirited resilience was finally broken in the closing stages.
Lively lightweight Nathan Dyer jinked away from Lynch to drive the ball goalwards and Blackstock was in sharply at the near post just ahead of Paul McShane to volley in Saints' winner.
The result was probably fair on the balance of play and chances created but the manner of defeat was still hard to swallow.
McGhee said: "Considering we had six players who probably would have been in the team not available to us I think we can be pleased with the performance but very disappointed with the result.
"We brought a little bit of pressure on ourselves at times towards the end, which was unnecessary, and almost invited them to win the game.
"I think we have found a future player in Joel. We know he has got potential and I thought he was fantastic. Kerry was terrific as well and, although Mark McCammon is still not as much of a goal threat as we would like him to be, he led the line brilliantly."
If only Albion could afford, or attract, a goal threat like Dexter Blackstock.
- Albion (4-4-2): Chaigneau 8; El-Abd 7, McShane 7, Butters 8, Lynch 8; Carole 6, Carpenter 7, Mayo 8, Frutos 8; Robinson 8, McCammon 8. Subs: Jarrett for Robinson (withdrawn 79), Gatting for Carole (withdrawn 90), Kuipers, Cox, T. Elphick.
- Southampton (4-4-2): Niemi; Baird, Hajto, Kenton, Cranie; Dyer, Folly, Quashie, Belmadi; Blackstock, Best. Subs: Ormerod for Best (withdrawn 46), Prutton for Cranie (withdrawn 64), Mills for Kenton (injured 67), Smith, Walcott.
- Matchfacts
- - Shots on goal: Albion 3 Southampton 8.
- Shots off goal: Albion 1 Southampton 6.
- Corners: Albion 2 Southampton 14.
- Offside: Albion 3 Southampton 7.
- Free-kicks: Albion 13 Southampton 14.
- Albion bookings: None.
- Southampton bookings: None.
- Albion scorer: Mayo (21).
- Southampton scorers: Blackstock (10), (86).
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