Liverpool lost their unbeaten Premier League record after Dejan Lovren scored the only goal of the game to give Southampton a surprise 1-0 victory at Anfield on Saturday.
The Croatia international headed in from a corner in the 53rd minute and contributed with a solid display at the back as Liverpool were unable to break down a determined Southampton back line.
Liverpool captain Steven Gerrard twice threatened with free-kicks, but that was the closest the hosts went in a frustrating game for manager Brendan Rodgers after his side's impressive start to the season.
Rodgers made three changes from the Liverpool side that drew 2-2 at Swansea City, as Brazilian playmaker Philippe Coutinho was ruled out with a shoulder injury and replaced by Iago Aspas.
Rodgers also rejigged his defence to include four centre-backs as Daniel Agger and Kolo Toure came in for Andre Wisdom and Jose Enrique, who both dropped to the bench.
Southampton were unchanged from their goalless draw against West Ham United last weekend, meaning Rickie Lambert and Dani Osvaldo led the line with support from Adam Lallana and Jay Rodriguez.
Liverpool started positively, Daniel Sturridge teeing up Jordan Henderson on the edge of the penalty area, but the Reds midfielder put his shot straight at Southampton goalkeeper Artur Boruc.
Rodgers was incensed with referee Nigel Swarbrick after an early challenge on winger Victor Moses from Saints right-back Nathaniel Clyne went unpunished.
Liverpool were presented with a free-kick in a dangerous position on the edge of the penalty area when Jose Fonte fouled Aspas in the 20th minute.
Gerrard curled the a shot over the wall from the set-piece, only for Boruc to scramble across goal and produce a diving one-handed save.
Sturridge felt aggrieved shortly afterwards when he went to ground inside the penalty area under a challenge from Lovren, but Swarbrick waved away the penalty appeals.
Moses was at the heart of Liverpool's attacking intent and he created a goalscoring opportunity out of nothing on the half hour when he broke through the Southampton defence, but failed to lift the ball over Boruc.
Rodgers withdrew Aspas, who had struggled to make much of an impact, at half-time and introduced England winger Raheem Sterling to give the home side more impetus in the final third.
But Liverpool's defence were almost punished early in the second period when Lallana intercepted a pass from Agger and sent Lambert clear, only for the Saints striker to be denied by Simon Mignolet.
Despite their obvious height advantage at the back, Liverpool conceded from a Lallana corner eight minutes into the second half.
Lovren outmuscled Agger as the pair challenged for a high ball to the back post and the Southampton defender saw his downward header cross the line despite Henderson's last-ditch attempt to clear.
The Reds were almost punished again moments later when Osvaldo found space on the edge of the area, but Mignolet reacted did well to save his low drive.
Gerrard continued to look Liverpool's mostly likely source of a goal and Boruc beat away a stinging free-kick from the Reds skipper on the hour-mark.
Southampton should have increased their advantage seven minutes later when Mignolet was forced to make a double save after left-back Luke Shaw had burst into the box.
Rodgers threw on Luis Alberto and Jose Enrique in a bid to get the hosts back in the game.
But despite long spells of pressure in the remainder of the contest, they were unable to find a way through as Southampton packed men behind the ball and held on to claim a deserved victory.