The 30-year-old's last appearance in a Reds shirt came in Liverpool's 3-2 loss at home to West Bromwich Albion in the FA Cup on 27 January.
The Belgium shot-stopper was replaced by Loris Karius - now at Besiktas - at the turn of the year after coming under criticism for poor performances for the first half of the season.
Mignolet is now set to get his first start for the Reds in eight months - with Liverpool's new no. 1 Alisson being given a rest.
“The only position I will confirm today is Simon (Mignolet) will start,” Klopp said. “He's been brilliant for me.
“All the rest you gave to wait until tomorrow but it will be a good team, I can tell you that. We are really competitive, we really want to win this game.
“I will make decisions. It [the changes] will not be nil and won't be 11. With our rhythm we are used to playing three times a week so let's do it.”
Klopp also confirmed that Dejan Lovren is close to making a return after coming through unscathed in four training sessions ahead of the game.
“Dejan looks actually quite good. He trained now 4 times and had a very intense period before that with fitness guys for 10 days, so he looks ready,” Klopp added.
Dominic Solanke is also back in training after picking up a knock for Liverpoo's U23s side and could make an appearance on Wednesday night.