Neil Warnock will be without Alan Tate and Jerome Thomas after both loanees played important roles in Leeds' recent upturn in form. The duo played for their respective parent clubs Swansea and West Brom in the earlier rounds of the competition.
Jason Pearce should come in at centre-back in place of Tate, while forward Luke Varney may get the chance to play on the left wing.
In a more defensive option, however, Sam Byrom could move into the midfield to allow Aidy White to fill in at left-back, with Lee Peltier switching to his favoured position on the right.
Frank Lampard played in the final of the Club World Cup after recovering from injury in the last fortnight and may be forced to play again in midweek with Ramires and Mikel both suspended and Romeu sidelined.
Benitez's problems in the centre could lead to a move forward for David Luiz, with the Spaniard testing the defender in the defensive midfield position twice since he took the reigns.
The game is likely to come too soon for John Terry, while there may well be starts for fringe players such as Bertrand, Marin and Sturridge, with Ross Turnbull in goal.
In their last 4 league encounters, dating back between 2002-2004, Chelsea failed to beat Leeds by more than a single goal, with the Whites picking up a win and a draw in the last two meetings between the sides at Elland Road.
Rafa Benitez will know that this will be the easiest cup for him to win in what may well be a short tenure with the club, though with Villa, Swansea or Bradford waiting in the semis, Leeds fans will also hope for glory after nearly a decade of hurt.
Chelsea are likely to rotate their squad where possible but the absence of their midfield battlers could play into the hosts' hands with the Championship outfit more than ready for the fight.
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