Frank Lampard's tenure as Blues boss got off to a nightmare start when they were beaten 4-0 by United at Old Trafford on the opening day of the season, although the fortunes of both sides have changed a lot since then.
Chelsea go into Wednesday's game off the back of seven successive victories across all competitions and will be favourites to take another step towards a second successive final against a United side that has struggled for form and goals since the two sides last met.
Here, Sports Mole looks at how the hosts could line up in West London.
Chelsea have some notable names on the treatment table at the moment, and none of them is expected to recover in time for this match, nor be risked if not 100% fit.
The continued absences of Antonio Rudiger and Andreas Christensen mean that Fikayo Tomori and Kurt Zouma will partner each other at centre-back again, but there is expected to be a change behind them with Willy Caballero coming into the team.
Fringe players such as Pedro, Reece James and Olivier Giroud could be handed a chance to prove themselves, with the latter battling for a starting role alongside Michy Batshuayi after both fell behind Tammy Abraham in the pecking order.body check tags ::