Chelsea came out 1-0 winners when the clubs met in a Barclays Premier League contest at the Etihad Stadium dominated by the west Londoners last week.
Saturday's rematch, also being played at Eastlands, has been given added spice by the apparent rivalry between the two managers, Manuel Pellegrini and Jose Mourinho.
Chelsea boss Mourinho has made a series of comments apparently deriding City on subjects such as financial fair play, transfer spending, refereeing decisions and disciplinary matters.
City's Pellegrini has largely refrained from getting involved in a war of words but hit back over Mourinho's remarks about referees and his claim Chelsea were the "little horse" in the title race.
Their latest clash is the pick of the four last-16 ties to be played on Saturday.
It remains to be seen how strong a side either manager wants to or can field.
Mourinho has injury doubts over first-choice central defensive pair John Terry and Gary Cahill.
Chelsea, however, do have the benefit of a seven-day break before their next fixture after the game, while City must prepare for the visit of Barcelona in the Champions League on Tuesday.
Pellegrini did hint at making changes for the game, but that was before his side's midweek clash with Sunderland was postponed, handing them an unexpected night off.
"It's important to give importance to the cup," the Chilean said last week. "But at this moment I have to decide which game will be more important and maybe it's Barcelona.
"Maybe we will put an alternative team out against Chelsea."
City are still expected to be without top scorer Sergio Aguero and midfielder Fernandinho but playmaker Samir Nasri has been back in training after a knee injury and could have an outside chance.
Saturday's action begins with another all-Premier League tie between Sunderland and Southampton at 12.45pm.
Wigan then continue their defence of the trophy at Cardiff and Championship sides Sheffield Wednesday and Charlton meet at Hillsborough.
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- Jose Mourinho
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