Saints became the latest victims of Leicester City's incredible Barclays Premier League title charge, as they fell to a 1-0 defeat at King Power Stadium.
Wes Morgan's header seven minutes before half-time separated the teams in what was a closely-fought encounter.
Saints, who had been aiming to make it three league wins in a row, could have gone in front shortly before Morgan's winner, but Sadio Mané was unable to convert their best chance of the game when clean through on goal.
The result leaves Ronald Koeman's side seventh in the table, still in the race for a European spot, ahead of their final six games of the season.
Koeman made four changes to the team that started in the 3-2 win over Liverpool, bringing in Victor Wanyama and Mané, who both had such a big impact in that famous turnaround against the Reds. Also restored to the line-up were Matt Targett and Cédric, as the Saints boss deployed both as wing-backs in a 3-5-2 formation.
Dropping to the bench were Oriol Romeu and Dušan Tadić, while Shane Long missed out through injury and Cuco Martina did not make the squad. Jay Rodriguez and Charlie Austin both took up places on the bench after injury lay-offs.
There was an electric atmosphere inside King Power Stadium, with the Foxes starting the day four points clear at the top of the table. As if things weren’t already good enough for their fans, the club’s chairman had also laid on free beer and doughnuts for them at the match.
Little surprise then that there was an enormous roar as the two teams emerged from the tunnel before kick-off.
The start of the game rather matched the frenetic atmosphere inside the stadium, but the energy levels were not quite matched with the appropriate quality.
Leicester gave Saints a couple of early problems, with José Fonte twice making excellent sliding interceptions to deny Shinji Okazaki, first from a low Jamie Vardy ball and then from Riyad Mahrez’s prodded delivery, but the hosts were unable to carve out a clear-cut opportunity.
Saints first real effort arrived in the 29th minute, as Davis spread the ball wide to Cédric, who sent in a first-time cross that picked out Pellè, but he sent his thumping header a yard or two over.
The chance started a seven-minute spell of intense pressure from the visitors, who should have led after 32 minutes when Mané burst clear and rounded Kasper Schmeichel, only to then hit his shot straight at the back-tracking Danny Simpson. The ball did hit the Leicester defender’s arm, but referee Michael Oliver ruled it was unintentional.
Fonte then nearly gave Saints the lead with what would have been one of the team’s goals of the season, as he unleashed a 30-yard rocket that was heading for the top corner, only for Schmeichel to make a stunning, one-handed save to tip it over, while Jordy Clasie then sent an angled shot from the edge of the area fizzing a yard above the bar.
It looked as if Saints might be about to make the breakthrough, but Leicester then went down the other end and took the lead themselves, as Christian Fuchs whipped in a beautiful ball from the left and Morgan rose highest to thump a header past Fraser Forster, sending the home crowd wild.
Koeman made one change at the break, bringing on Tadić for Targett and switching to a 4-2-3-1 system.
Saints were nearly in trouble within seconds of the restart, as Vardy pounced on a loose ball and threatened to break clear, only to be brought down by Wanyama, whose punishment was limited to a yellow, as a couple of other defenders were also in the proximity. Leicester’s Drinkwater went into the book as well shortly afterwards, for a foul on Tadić.
The hosts nearly went 2-0 up just after the hour, as Fonte slid in to intercept a Drinkwater cross from the right, only to send the ball looping over the head of Forster, who back-tracked to brilliantly claw the ball away to safety.
Forster again came to the rescue after 71 minutes, making a superb close-range save from Simpson, after Vardy had got to the by-line and prodded the ball to him in space at the back post, just six yards out.
After Koeman made a double change, sending on James Ward-Prowse and Austin for Clasie and Davis, Forster denied Vardy at the near post in the 85th minute.
But Saints could not bridge the gap, as their run of consecutive Premier League wins ended at two, while Leicester went seven points clear at the top with six to play.
Leicester City (4-4-2): Kasper Schmeichel; Danny Simpson, Wes Morgan (c), Robert Huth, Christian Fuchs; Riyad Mahrez (Demarai Gray 79), N’Golo Kanté, Danny Drinkwater, Marc Albrighton (Nathan Dyer 90); Shinji Okazaki (Leonardo Ulloa 63), Jamie Vardy. Unused substitutes: Mark Schwarzer (GK), Marcin Wasilewski, Daniel Amartey, Andy King.
Goal: Morgan (38).
Booked: Drinkwater, Fuchs.
Southampton (3-5-2): Fraser Forster; Virgil van Dijk, José Fonte, Ryan Bertrand; Cédric, Steven Davis (James Ward-Prowse 73), Jordy Clasie (Charlie Austin 73), Victor Wanyama, Matt Targett (Dušan Tadić 46); Sadio Mané, Graziano Pellè. Unused substitutes: Maarten Stekelenburg (GK), Maya Yoshida, Oriol Romeu, Jay Rodriguez.
Booked: Wanyama, Tadić.
Referee: Michael Oliver.