Skrtel, who had not played a senior game since December, replaced him, before a brace from Sadio Mane inspired the Saints to a shock comeback victory.
"How many times does a Premier League team score three in a half? Not many," he told the Liverpool Echo. "There are clearly areas that Jurgen Klopp has to address for next season.
"Southampton made changes as you'd expect but taking off Dejan Lovren seemed to be a turning point.
"He'd done really well and was helping keep Simon Mignolet and the whole of the defence calm but Martin Skrtel who replaced him has been out of the team for such a lengthy period, he didn't adjust to the pace of the game and was too busy having to concentrate on himself."
Klopp's side stay ninth in the Premier League table.