The Reds host the Championship outfit looking to extend their unbeaten run in all competitions to 15 games off the back of the weekend's Premier League win over Sunderland.
That win keeps Liverpool only a point off of first-placed Chelsea but came at a price, with Philippe Coutinho stretchered off with an ankle injury in the first-half and having to leave the stadium on crutches and with his right foot in protective casing.
The length of the Brazilian's lay-off is expected to be determined later on Monday, with the attacking midfielder having undergone scans in hospital earlier in the day.
Jürgen Klopp also has a number of other injury concerns, with Adam Lallana and Daniel Sturridge struggling with groin and calf injuries and Roberto Firmino suffering a knock late on against Sunderland.
Sturridge and Lallana are both unlikely to feature in the manager's plans to face Leeds, with neither having yet to return to training.
The German won't take any risks with another potentially tricky league tie awaiting at Bournemouth on Sunday, and so Firmino - who took a blow to the calf late on before being substituted - is also unlikely to feature.
Origi in line to start after Sunderland strike
Having made wholesale changes for the previous round's home victory over Tottenham Hotspur, he is expected to turn to the fringe players - and even a handful of Academy prospects - for the visit of Garry Monk's men.
First-choice goalkeeper Loris Karius will make way for Simon Mignolet, with the defence that faced Spurs - Trent Alexander-Arnold at right-back, Alberto Moreno at left-back and Lucas Leiva and Ragnar Klavan at centre-back - all in the frame to start.
Further ahead, Klopp's usual midfield make-up of Jordan Henderson, Emre Can and Georginio Wijnaldum could be replaced by the likes of Marko Grujic, Kevin Stewart and the promising Ovie Ejaria.
Those three featured alongside Wijnaldum in the previous round, as Klopp changed his set-up to accommodate both Sturridge and Origi in their preferred central striking roles.
But he is more likely to field the 4-3-3 system with which he has frequently set up his side this season, meaning Origi could continue his run of starting in every game of the competition this term.
The Belgian, who scored his first Premier League goal of the season and his first since April with his strike in the 2-0 victory over Sunderland.
Sheyi Ojo could return to the matchday squad for the first time this season after returning to training from a back injury earlier this month, with Cameron Brannagan another potential option unless Klopp decides to keep Sadio Mane or Firmino in the front three.
Highly-rated Academy forward Ben Woodburn could also be in line for a cameo. The Welsh youth international made his senior debut at 17 years and 42 days to become the third-youngest player ever to play for the club by playing the final minutes of the weekend's win over the Black Cats.