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And Liverpool fell behind 33 points, on goal difference, from Manchester United, which has a postponed match against Burnley on 12 January.
Leicester City is third with 31 points, while four teams have 29 points, including Manchester City, which also have two postponed games, and if they win, they can mathematically skip Liverpool.
At St Mary’s Stadium on the South Coast, Southampton finally settled their grueling contract by beating Liverpool with a goal from former late striker Danny Ings just two minutes later.
Southampton was the surprise of this season, losing in the last six games to Liverpool in the league and losing their net with 17 goals and scoring just two.
Southampton entered the game without a win in the last four games (3 draws and 1 loss), while Liverpool drew in their last two games with West Bromwich Albion and Newcastle.
The loss is also the first for Liverpool since their resounding loss to Aston Villa 2-7 last October.
Thiago Alcantara played his first major game for Liverpool since the derby on 17 October.
Liverpool played without two original defenders and German coach Jürgen Klopp entrusted the task to Brazilian Fabinho and captain Jordan Henderson.
Liverpool suffer several injuries in this streak, including the Dutch Virgil Van Dyck, the Cameroonian Joel Matip and Joe Gomez.
Southampton lost two influential players, striker Che Addams, who suffers a concussion, and defensive midfielder Oriol Romeo with a calf injury. In addition to the absence of goalkeeper Alex McCarthy, due to his contagion with the new Corona virus.
Just two minutes after kick-off, Southampton opened the scoring for scorer Ings, who took advantage of an Internet error Alexander-Arnold and passed the ball over Brazilian goalkeeper Alison.
The goal is number 50 in the English Premier League in 124 games, and the seventh this season.
Liverpool’s reaction was relatively timid and a first chance came through their Senegalese striker Sadio Mane, who fired a ball from the outskirts of the region over the crossbar (27), and then another attempt by Egyptian Mohamed Salah, but goalkeeper Frazier Forster intervened at the right moment (30).
Southampton formed danger with quick counterattacks without exploiting any of them.
In injury time in the first half, Salah raised his header from close range, but crossed the crossbar.
Liverpool pressed hard early in the second half, hoping to equalize, but failed to hit the first ball between the three posts only in the 75th minute for Manet.
Manet was not in his day because he wasted two other occasions, the first when he accelerated the shot (81), and the other with a header in the final seconds that went over the crossbar.