Jurgen Klopp's side improved as the match wore on but found their efforts thwarted time and time again by a resolute Southampton defence.
Thiago Alcantara was including in the starting lineup for the first time since October, but like the rest of his teammates, the Spaniard struggled to have his desired impact on proceedings.
The loss means the Reds stay top of the table, albeit only on goal difference, and with arch-rivals Manchester United having a game in hand.
Whilst Liverpool were poor on the night, credit must go to the Saints who executed their game plan to perfection and deserved to get something from the game.
Here's what Klopp had to say, with a full transcript available from liverpoolfc.com
On refereeing decisions
"What Andre Marriner did with Sadio Mane tonight, I'm not sure that's okay. Man United had more penalties in two years than me in five and a half years, but no excuses for tonight."
"It looked like a clear penalty. I turned around to the 4th official and asked if it would be checked. He said: 'We've checked it already, no pen.''
On concerns with his side
"Of course we worry. We are not silly. We have to show a reaction 100%. Southampton deserved it. They ran their socks off."
On the performance
"Very frustrating because it was so unnecessary. Our decision making was not good, it was the last pass. Our fault, my responsibility."
"If you play like you did tonight against a team like Southampton, you play with fire. We don't score late goals because we have in the past. We do that because we put you under pressure. Southampton coped with that but we helped them. We were not good tonight."