Match ends, Southampton 4, Manchester City 2.
Manchester City's hopes of qualifying for the Champions League remain in the balance as a brilliant Sadio Mane hat-trick secured Southampton an easy win.
Shane Long struck at the near post and Mane doubled the lead from 10 yards before City's Kelechi Iheanacho scored.
Mane then pounced twice to make sure of the win - reacting quickly as Jose Fonte's header came off the crossbar and converting Dusan Tadic's pass.
Iheanacho found the top-right corner late on but the match was all but over.
The victory ensures Southampton - two points adrift of sixth-place West Ham with two games remaining - can still qualify for next season's Europa League.
City remain fourth - three points behind third-placed Arsenal and four ahead of fifth-placed Manchester United, who drew against leaders Leicester at Old Trafford on Sunday.
Manuel Pellegrini's team still have a comfortable cushion over their city rivals, but face a defining week, with the second leg of their Champions League semi-final against Real Madrid on Wednesday followed by a tussle with Arsenal in the league four days later.
City make changes with eye on Real
Pellegrini had said it was "unbelievable" that the Premier League had refused to move this late kick-off forward to aid his team against a Real side who have had 24 hours extra rest after playing on Saturday.
What was also unbelievable was the ease with which Southampton created chance after chance against a fragile City defence.
Having secured a 0-0 draw at home against Real, the Champions League semi-final is evenly poised, but this defeat - their 10th in the league - and the manner of it will not be ideal preparation.
It was no surprise that the Chilean had freshened up his team - with five changes from the team who thumped Stoke, and eight from the side who drew against Real.
Top scorer Sergio Aguero remained on the substitutes' bench, while Yaya Toure - who returned to training on Friday after injury - and captain Vincent Kompany were not in the squad.
The trio will no doubt strengthen City when they return - with the club's fans hoping they are back for the trip to Madrid.
Southampton dominate, City flounder
For incisiveness, and for chances created, there was only one team in it. Southampton sprayed the ball around with ease, particularly punishing their visitors on the counter-attack.
City had their moments; Raheem Sterling was denied from six yards thanks to a wonderful point-blank save by Fraser Forster with the score goalless, while Iheanacho halved the deficit as he took advantage of a woeful Cuco Martina clearance.
The 19-year-old Nigerian striker collected his second brilliantly from the edge of the box for a goal which suggests he has a bright future ahead.
But for the majority of the match, and the first half especially, Saints ran amok. Long twice caused City's backpedalling defence problems before he toe-poked Tadic's hooked byline cross into the near post.
Saints had nine shots at goal in the opening 45 minutes, compared with City's three, and their second once again highlighted the visitors' lackadaisical approach to defending. The hosts burst forward at pace and the influential Tadic set Mane free to side-foot home.
Southampton's superiority deserved a greater lead, but early in the second half their two-goal advantage was restored just when City had threatened to change the momentum of the match.
Fonte headed Steven Davis' corner on to the crossbar and it was Mane who reacted quicker than anyone else, sticking his foot out from two yards.
Southampton continued to threaten. Virgil van Dijk forced Joe Hart into a fine save with an audacious scissors kick before Mane got his third to become the sixth player to score a Premier League hat-trick against City.
Man of the Match - Sadio Mane
What the managers said
Southampton boss Ronald Koeman: "It was a great game - and maybe the best opening 45 minutes by us of the season. We scored some great goals.
"We created so many problems for them. The pace was the key to win the game. Sadio had a big impact in the result. We did an amazing job.
"We have a team of players really motivated and we like to play good football. We fight for Europe and that's what we like. Two games to go and we're still fighting for something."
Manchester City manager Manuel Pellegrini: "I'm very frustrated because I didn't expect that performance, especially in defence. At least four of them [today's line-up] are not playing [regularly].
"I think we could've played on Saturday and named a stronger team, but in this case we had to prioritise Wednesday's game.
"The best way to prepare is to win but we couldn't do it."
The stats you need to know
- Southampton have scored four or more goals in consecutive Premier League games for the first time.
- Manchester City have conceded four or more goals in three Premier League games this season, the most since the 00/01 campaign (4+ in six games).
- Sadio Mane has scored seven goals in his last six Premier League games for Southampton; which comes after a run of 19 league appearances without scoring.
- Kelechi Iheanacho has averaged a goal every 86.9 minutes in the Premier League this season. It's the best rate of any player who has scored two or more goals.
- Dusan Tadic is only the fourth player to have have managed three or more assists in two different Premier League games (after Eyal Berkovic, Cesc Fabregas and Thierry Henry).
Manchester City travel to Madrid on Wednesday for their Champions League second-leg semi-final tie against Real before a Premier League match against top-four rivals Arsenal on 8 May. Southampton will visit Tottenham on 8 May.
- 6José Fonte
- 17van Dijk
- 4ClasieBooked at 30minsSubstituted forRomeuat 59'minutes
- 8DavisSubstituted forWard-Prowseat 73'minutes
- 11TadicBooked at 54minsSubstituted forRodriguezat 87'minutes
- 2Cédric Soares
- 25FernandinhoBooked at 20minsSubstituted forDemichelisat 60'minutes
- 18DelphSubstituted forNavasat 64'minutes
- Andre Marriner
- Shots on Target
Second Half ends, Southampton 4, Manchester City 2.
Wilfried Bony (Manchester City) wins a free kick in the attacking half.
Foul by Victor Wanyama (Southampton).
Hand ball by Raheem Sterling (Manchester City).
Foul by Aleksandar Kolarov (Manchester City).
Sadio Mané (Southampton) wins a free kick in the defensive half.
Jesús Navas (Manchester City) wins a free kick in the attacking half.
Foul by Ryan Bertrand (Southampton).
Substitution, Southampton. Jay Rodriguez replaces Dusan Tadic.
Raheem Sterling (Manchester City) wins a free kick on the left wing.
Foul by Cuco Martina (Southampton).
Attempt blocked. James Ward-Prowse (Southampton) right footed shot from outside the box is blocked. Assisted by Shane Long.
Foul by Martín Demichelis (Manchester City).
James Ward-Prowse (Southampton) wins a free kick in the defensive half.
Nicolás Otamendi (Manchester City) wins a free kick in the defensive half.
Foul by Dusan Tadic (Southampton).
Goal! Southampton 4, Manchester City 2. Kelechi Iheanacho (Manchester City) left footed shot from outside the box to the top left corner. Assisted by Jesús Navas.
Foul by Pablo Zabaleta (Manchester City).
Sadio Mané (Southampton) wins a free kick in the attacking half.