Blues boss Di Matteo was always likely to consider resting the midfield duo, given the number of changes the club traditionally make for League Cup ties.
But he also had to take into account their emotional state after it emerged they were the players Chelsea accused referee Mark Clattenburg of using "inappropriate language" towards during Sunday's explosive Barclays Premier League game against United.
It was unclear on Tuesday night whether either would prefer to sit out Wednesday night's revenge mission, which takes place against a backdrop of yet another racism saga that threatens to drag English football through the mud.
Clattenburg, who faces police and Football Association investigations, is understood to categorically deny any wrongdoing.
The official in the middle of what could be a febrile atmosphere at Stamford Bridge on Wednesday is Lee Mason, who United boss Sir Alex Ferguson jokingly wished "Good luck!" even before the serious allegations about Clattenburg emerged.
That was because of the decision by Sunday's referee to send off two Chelsea players and failure to spot Javier Hernandez's winning goal should have been disallowed for offside.
By accident or by design, the atmosphere on Wednesday could be helped by the likelihood of both sides making a raft of changes for the fourth-round clash.
Fernando Torres and Branislav Ivanovic are both suspended following their red cards on Sunday, with John Terry is also banned.
Ashley Cole was likely to be among those rested and is suffering with an ankle problem anyway, while Frank Lampard remains out.
"It is certainly a tricky situation," Di Matteo told his club's official website.
"It is also our fourth game in 10 days and they have all been big games, so we are looking to freshen the team up a little bit for sure, and also put a couple of youngsters in.
"We always talk about developing and giving youngsters a chance so this type of game is a good opportunity for some of them."
Daniel Sturridge, Cesar Azpilicueta and Lucas Piazon - who has shaken off a hamstring strain - all look certain to start.
They could be joined by Victor Moses, Marko Marin, Oriol Romeu and Ryan Bertrand if Mikel and Mata are given a breather, and youngsters George Saville and Nathan Ake may also be included in the first-team squad.
Di Matteo said of his fringe men: "They are very good players and they are young but they have a little bit of experience as well, and it will be great to see them perform.
"They have been waiting for an opportunity and going forward I think we will see more of them.
"Our fixture list is pretty packed with seven games in November and nine or 10 games in December and it is very demanding.'
Like Chelsea, United fielded a blend of youth and experience in their third-round win last month.
"We will have to wait for the teamsheet, but I am not expecting just a young team, I am expecting a strong team," said Di Matteo, who was expecting both sides to be as hungry to win on Wednesday as they were on Sunday.
"When you play Man United it is always a big game in whichever competition you play in.
"I hope the supporters get behind the team, the young players especially, and push us on to a win.
"Any trophy you add to your cabinet is a plus and this is one you have to try your best to go and get. That is the objective."
Monday saw Di Matteo named on a 10-man shortlist for FIFA's World Coach of the Year award.
The Italian was disappointed Didier Drogba was the only member of his Champions League-winning squad nominated for the FIFA Ballon d'Or but added: "It is a privilege to be the manager of Chelsea and to work with these world-class players, trying to achieve success."