Jose Mourinho's side are exceeding expectations by keeping pace with Jurgen Klopp's side at the top of the table, in what is one of the tightest title races in years.
During the draw against Fulham, Liverpool were forced to play without any recognised centre-back in the second half after Joel Matip was forced off with a back injury at half-time. Jordan Henderson and Fabinho paired up for the second period as the champions fought back for a draw at Craven Cottage.
Klopp revealed that Matip could be fit enough to return against Spurs, but if not it could present a chance for either Rhys Williams or Nathaniel Phillips.
Diogo Jota will miss two months of action after picking up an injury in the Champions League last week.
He joins Virgil van Dijk, Thiago, Joe Gomez, James Milner, Xherdan Shaqiri, and Naby Keita on Liverpool's extensive injury list.
For Tottenham, Gareth Bale missed the weekend match against Palace due to illness but is expected to be available from the bench again for the game at Anfield.
Erik Lamela is the only senior player expected to miss out for Spurs, with Mourinho having a lot more players at his disposal than Klopp for the match on Wednesday.
Star duo Heung-min Son and Harry Kane will start after once again linking up effectively against Crystal Palace, with Kane on the receiving end of an assist on this occasion.