The Reds stormed to a landslide victory when the clubs faced each other in the quarter-finals of the Capital One Cup at St Mary’s in December.
Former Liverpool and Saints manager Souness believes that result is one that Ronald Koeman’s side will be desperate to avenge.
“No two games are the same,” Souness told saintsfc.co.uk. “I think Southampton will be looking forward to an opportunity to lay that ghost to rest if you like.”
Souness added: “Southampton should be looking forward to the game, having turned over Stoke in their last match, so they’ll be fancying themselves. They hit the wall a bit, but he (Ronald Koeman) has got them going again and no one gets an easy ride at Southampton – other than Liverpool in the League Cup.”
The three-time European Cup winner also believes the outcome of Liverpool’s Europa League tie with Manchester United tomorrow could also have a significant bearing on Sunday’s match.
Jürgen Klopp's side visit Old Trafford holding a 2-0 lead from the first leg of their last-16 tie.
“They’ve been quite unpredictable,” Souness said of Liverpool. “I think Southampton supporters saw them at their very best in that League Cup game.
“They’ve been inconsistent and that’s why they’re not challenging for the Premier League.
“It really depends what Liverpool turn up. They could be tired and feeling sorry for themselves having been turfed out of the Europa League, or their tails could be up because they’ve gone to United and done the business.
“Psychologically they could be slightly damaged, or psychologically they could be flying.
“Then there’s the question of how fresh will they be going into the game, having played on the Thursday and Southampton having not played.”