The centre-back has aggravated a knee injury in training and is set to miss the Europa League last-32 second-leg clash, while Fabio Borini has been ruled out for six to eight weeks
The Slovakia international was an unused substitute in Liverpool’s 5-0 win over Swansea on Sunday, and a knee injury looks set to rule him out of the second-leg tie against the Russian champions.
"Skrtel is being assessed," Rodgers said in his pre-match press conference. "I think he'll struggle with his knee, he had a knock on it and he tried to train and made it worse. It's highly unlikely he'll play."
The injury to Skrtel means Jamie Carragher and Daniel Agger are expected to continue in the centre of defence against Zenit.
Elsewhere, injury-plagued striker Fabio Borini is set to miss up to two months of the season after sustaining a dislocated shoulder in Sunday’s win against Swansea.
“By the weekend, he’ll look to have an operation and you’re then looking at six to eight weeks,” revealed Rodgers.
“It’s been a difficult season for Fabio, coming into such a big club, getting injured early on, coming back and then working hard for his moment and doing his shoulder.
“It’s been difficult for him but he’s a tough-minded young boy and he’ll get through the op well and we’ll see how he recovers.”