The Reds were already struggling for numbers in the middle of the park before Sunday's memorable mauling of Manchester United, with Fabinho missing out due to a knock and Thiago Alcantara and Harvey Elliott both longer-term absentees.
However, James Milner sustained a hamstring injury after less than half an hour, and Naby Keita was stretchered off after being on the end of Paul Pogba's two-footed challenge which earned the Man United man a red card.
All five midfielders will miss out in midweek, meaning that Klopp may be forced into sticking with the same trio that ended the game at Old Trafford - Jordan Henderson, Curtis Jones and Alex Oxlade-Chamberlain.
Origi is expected to lead the line having scored 10 goals and assisted two more in his last nine EFL Cup starts, and he could be joined in the attacking three by Sadio Mane following his surprise exclusion from the starting lineup at Old Trafford.
Should Klopp decide to rest Mane again ahead of a big week next week then youngster Kaide Gordon could get another chance in the first team, having started in the previous round against Norwich City.
Like Mane, Joel Matip was a surprise exclusion against Man United and therefore could start alongside Gomez at the heart of the defence at Deepdale, although Nat Phillips provides another option for the visitors.
Liverpool possible starting lineup: Adrian; N Williams, Gomez, Matip, Tsimikas; Oxlade-Chamberlain, Henderson, Jones; Minamino, Origi, Mane