Fraser Forster denied James Milner from the spot and Liverpool of all three points, as their bid for Champions League took a subtle hit.
Jack Stephens was adjudicated to have handled the ball inside the area, but Forster held firm pushing aside the penalty with a strong right hand.
The Southampton goalkeeper then kept out Marko Grujic’s header late in stoppage time to preserve a goalless draw at Anfield.
Liverpool, who has not scored against Southampton in four attempts this season, leads fifth-place Manchester United by five points with two games remaining. United, however, has two in hand.
A match largely void of excitement was brought to life when Liverpool was awarded a penalty after it was adjudicated that Jack Stephens had handled the ball in the area.
But following yellow cards for unsportsmanlike conduct to Cedric Soares and James Ward-Prowse, Milner had his attempt from the spot saved as he looked for the bottom left corner.
Philippe Coutinho, Daniel Sturridge and Adam Lallana all had half chances over the final quarter-hour, but none concerned Forster enough.
The Saints’ shot stopper had one last act of brilliance to ensure his team left with a point, as he was able to lift Marko Grujic’s goal-bound header over the bar.
Liverpool: Mignolet, Clyne, Lovren, Matip, Milner, Lucas (Lallana 69), Winjaldum (Grujic 87), Can, Coutinho, Firmino, Origi (Sturridge 69).
Unused subs: Karius (GK), Moreno, Alexander, Klavan.
Bookings: Lovren (89).
Southampton: Forster, Bertrand, Yoshida, Stephens, Cedric, Romeu, Davis, Ward-Prowse, Romeu, Tadic, Boufal (Redmond 61), Gabbiadini (Long 69).
Unused subs: Hassen (GK), Pied, Caceres, Hojbjerg, Rodriguez.
Bookings: Cedric (65), Ward-Prowse (65), Bertrand (90+2).