The former Dortmund head coach has continually complained about the hectic scheduling his team has to contend with this season, and that combined with a list of injuries means that he is unlikely to take a chance with any of his key players as Liverpool continue to fight to retain their title, as well as pursue Champions League glory.
In terms of injuries, Virgil van Dijk, Diogo Jota, Joel Matip, Naby Keita, Joe Gomez and Konstantinos Tsimikas are all still unavailable, which should help Klopp with his selection decisions in some areas.
Caoimhin Kelleher impressed as a stand-in for Alisson earlier in the season and should be given another run-out in goal, potentially in front of an entirely new back four.
Neco Williams, Nathaniel Phillips, and Rhys Williams could all feature, with James Milner deputising for Andy Robertson at left-back.
Curtis Jones was rested from the starting XI for the loss against Southampton, with Thiago coming in as his replacement. These two could actually play together versus Villa, though, with Alex Oxlade-Chamberlain making up the final position in the midfield three.
In previous seasons in the FA Cup, Klopp has tended to use the round to give star players a rest, and that will probably be the case again here, so expect two or all of Sadio Mane, Mohamed Salah, and Roberto Firmino to feature on the bench.
With Jota out injured, that will mean a front three of Xherdan Shaqiri, Divock Origi and Takumi Minamino.