Saints dropped into the relegation zone for the first time under Glenn Hoddle as a result of this defeat - but not because of it.
Taking a beating at Old Trafford - even by five goals - is no disgrace and no disaster in the the survival equation.
Far more damaging was needlessly losing at home to the blue half of Manchester five days earlier - and the two other Dell defeats to poor opposition, and the six points already carelessly thrown away on the road this season.
Those are the reasons why Southampton now find themselves in the bottom three rather than the fact they lost a game which encapsulated many of their plus points - and their failings.
They moved the ball around sweetly and were on top for much of the first half - but they lacked any cutting edge in front of goal and they gave away silly goals. Sounds familiar..?
Looking for a positive side to the convincing scoreline, Hoddle can legitimately point to the fact that his side had most of the play in the first half and probably deserved to go in level at the break.
But, for all their possession, they never really hurt United who looked distinctly out of sorts following their midweek Champions League set-back.
And in any case their whole gameplan was effectively wrecked after just eight minutes by a howler which will haunt poor Paul Jones, who emulated Massimo Taibi's concession of an almost identical goal at the same end of the ground in last season's corresponding game.
They say what goes around comes around and the sad thing is that Saints fans can no longer gloat at Taibi's blunder in letting a harmless shot squirm through his legs.
The surface was a lot more greasy this time but that was all the more reason to be vigilant as andy Cole spun and hit a low drive from 25 yards. It looked a straightforward pick-up but somehow it slipped through the keeper's legs.
United have never lost after taking the lead in the Premiership so it was almost a case of game over before it had properly begun.
To be fair Saints did not let their heads drop but set about reclaiming the initiative which they were just beginning to seize when they fell behind.
They closed down well in midfield, forcing the home side to put passes astray but, while stringing five across the middle enabled them to gain possession, it meant there was all too often no-one forward enough to capitalise.
Consequently they frequently resorted to long-range efforts, similar to that of cole. But for all his flamboyant eccentricities, Fabien Barthez took no risks and got solidly behind everything.
He stopped a Kevin Davies header and distance drives from Hassan Kachloul and Mark Draper who both also cleared the bar when well placed.
It was hardly panic stations for the champions but it would have been enough of a straw for Saints to cling to during the half-time team talk had they not conceded another during injury-time.
Renowned time-keeper Sir Alex Ferguson may like to explain how his team managed to score 70 seconds into stoppage time when the fourth official had signalled only one minute to be added.
But that would be to churlishly detract from a great finish by Teddy sheringham, who sweetly chipped into the top right corner from the left edge of the penalty area.
It was a supreme piece of vision to spot Jones stranded off his line and exquisite skill to beat him.
It was a goal which could only be scored by a man brimming with confidence after a roaring start to the season and one which merely increased the dejection of the Welsh international who was caught off his line.
That strike, and more crucially its timing, knocked the stuffing out of Saints who came out flat at the start of the second half.
Any faint hope Hoddle's men might have had of retrieving the game then vanished as Sheringham scored twice in the space of four minutes to complete his hat-trick.
The first on 50 minutes was a cracking 14-yard shot into the top left corner and the second was neatly steered into the bottom right from similar range.
But once again Southampton contributed significantly to their own downfall.
For the first Matthew Oakley was robbed in the centre circle by Paul scholes who swept wide for David Beckham to cross and catch the defence in disarray, expecting the side to be moving forward.
Then Jason dodd's ball forward was intercepted by Nicky Butt ahead of the sluggish Jo Tessem. Again the defence was caught unprepared and Cole laid off for his strike partner to finish.
The south coast side also shot themselves in the foot for the fifth on 71 minutes. the goal itself was well executed with Beckham's left-wing corner flicked on by Scholes at the near post for Cole to nod home at the back stick.
But the fault lay in the way that the corner was conceded. Tahar El Khalej had been robbed in front of his own goal by cole who was just about to score when Dodd somehow got across to make a fine block.
To their credit, Saints never stopped trying to play football and they did not give up, even though the game had clearly gone.
And they almost got one back when Kachloul put James Beattie in on goal. It was the third season in succession that he had had a golden chance to score at Old Trafford and, for the third time, he failed to make it count, Barthez rushing from his line to block the flick shot.
It could have been worse for Southampton though. Ryan Giggs crashed a right-foot shot against the underside of the bar and, in the final minutes, Jones partially redeemed himself with two world-class saves from Dwight Yorke.
The worrying thing for Saints - and the rest of the Premiership - is that the champions looked as though they had at least two more gears in reserve while Hoddle's men were going flat out and still not staying with them.
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