A convincing Blackburn win pushed Southampton further into the relegation mire at Ewood Park.
Morten Gamst Pedersen fired Rovers ahead from a narrow angle after Aaron Mokoena's raking pass picked him out.
Andreas Jakobsson deflected Steven Reid's cross into his own net, before the Republic of Ireland international converted Dominic Matteo's cross.
Southampton offered little attacking threat, with Henri Camara failing to capitalise on two first-half chances.
Blackburn boss Mark Hughes restored Paul Dickov to the starting line-up for the first time since 19 March and he proved his early nuisance value as he worked the inside-forward channels.
Dickov played no part, though, as Blackburn took an early lead.
Referee Barry waved away Southampton appeals for a foul on Graeme Le Saux and as they argued, Mokoena arrowed a long diagonal ball over Rory Delap for Pedersen to superbly beat Paul Smith from a narrow angle.
Claus Lundekvam bundles into fellow Norwegian Pedersen
Blackburn's five-man midfield not only gave them plenty of width, but Pedersen proved difficult to locate when he came in off the wing.
The Norwegian missed two good chances to stretch Rovers' lead before half-time.
He first produced an air-shot as David Thompson rolled the ball across the six-yard box and then headed over from six yards.
Southampton's two first-half chances both fell to Camara, who side-footed inches wide after a training-ground corner had opened Blackburn up, and his control then let him down after an astute Peter Crouch pass.
Saints' need to get something from the game saw boss Harry Redknapp replace Le Saux at half-time with Kevin Phillips to provide a three-man strike force.
But the ploy backfired almost immediately as Blackburn doubled their lead.
Reid exploited the space vacated by Le Saux to fire in a low cross which Jakobsson could only deflect past the stranded Smith.
Things got worse for Southampton as they failed to deal with Pedersen's corner and Matteo squared the ball back for Reid to hammer in a first-time shot from 10 yards.
Blackburn's appetite and desire gave no hint they had next week's FA Cup semi-final against Arsenal on their minds as their defensive solidity held firm.
Blackburn manager Mark Hughes: "I thought the players were magnificent, each of them put in a committed performance.
"It was important we got the three points and there were no signs they were thinking ahead to next week.
"We probably need one more win to be safe, and it's made it difficult for the teams below us to catch us."
Southampton boss Harry Redknapp: "That was the worst we have played for a long time, today was a big setback for us.
"But all teams have days like these and it's how you react to them that counts, so there's no point battering people.
"They have shown previously shown spirit and resolve every week and proved they can get out of this."
Blackburn: Friedel, Neill, Todd, Nelsen, Matteo, Mokoena, Thompson (Emerton 45), Reid (Stead 74), Flitcroft (Tugay 49), Pedersen, Dickov.
Subs Not Used: Amoruso, Enckelman.
Booked: Emerton, Reid.
Goals: Pedersen 11, Jakobsson 48 og, Reid 55.
Southampton: Smith, Delap, Lundekvam, Jakobsson, Bernard (Higginbotham 83), Telfer, Redknapp, Quashie, Le Saux (Phillips 45), Crouch, Camara (Anders Svensson 75).
Subs Not Used: Poke, Davenport.
Referee: N Barry (N Lincolnshire).