Neil Critchley will replace Jurgen Klopp in the Liverpool dugout as the eight time League Cup winners travel to Villa Park for only the third time to contest a domestic cup encounter.
Aston Villa narrowly missed out on three points against Liverpool's first team in the Premier League when Dean Smith's side led the league leaders 1-0 until the 85th minute in October.
Villa haven't won since late November, a 2-0 win over Newcastle which eased fears of filling a relegation place at Christmas. After three losses on the bounce, Villa now find themselves above the drop zone by only goal difference.
Liverpool have led the Premier League for some time now, but the U23 side that will travel to Villa Park currently occupy seventh place in Premier League 2.
The Reds advanced through the Round of 16 with a 5-4 penalty shoot-out victory over then Unai Emery's Arsenal who played out a 5-5 draw at Anfield. A host of youngsters impressed for Liverpool, but without any senior figures at Villa Park they'll be tested again.
Villa themselves beat West Midlands rivals Wolves 2-1 at Villa Park to advance to the next round.
Villa are expected to make a host of alterations, with Jack Grealish and John McGinn due to be rested, whilst Tyrone Mings remains out of selection until the new year.
Conor Hourihane will return to Dean Smith's squad after missing last weeks defeat at Bramall Lane through injury.
Liverpool's Rhian Brewster may miss out due to injury. U23 coach Critchley has no other injury problems to deal with, nor does he have any suspensions as he hands out many first-team debuts.
Liverpool's kids have nothing to lose and up against a second-string Villa team will likely be the more motivated of the two sides, all eager to prove a point.
Villa haven't been Liverpool at Villa Park since 2011, and in the League Cup, the Reds beat Villa 4-3 away from home to secure a semi-final place.
What the managers say
Dean Smith labelled the quarter final clash a 'free hit.' The Villa boss spoke to AVTV:
"We have to make sure we're really professional like we have been in this tournament so far and make sure we get into the latter stages.
"We're disappointed to have lost the last three games, two away and the one at home was a bit of a hiding against Leicester so we have to give the supporters something to shout about now."