Mancini would like to select an entirely different team to the one that drew 1-1 with Arsenal in the Premier League on Sunday.
City travel down to London on Saturday for another league game against in-form Fulham and, with the champions stuttering to three draws from their first five games, that is very much Mancini's focus ahead of Tuesday night's cup clash.
The Italian said: "We can't play with the same players. We need to recover because afterwards we have another hard game in London. We will change all the players if it's possible. We are unlucky with the draw because we always get difficult games."
The League Cup is the one domestic trophy Mancini has not won since taking over as City boss in 2009, with his best run coming last season when they lost to Liverpool in the semi-finals.
He added: "We want to win again the championship, that's our target. If we win also the Capital One Cup, then okay, but the target should be the championship again."
Mancini will include youngsters Denis Suarez, Abdul Razaq and Luca Scapuzzi in the squad while Carlos Tevez and Mario Balotelli are likely to lead the line after only being used as substitutes against Arsenal.
But City will be without four players after James Milner and Maicon joined Samir Nasri and Micah Richards on the sidelines.
Maicon took a kick to his leg against Madrid and is unlikely to be out for long but Milner was due to see a specialist on Monday about a toe problem.
Several players will get the night off completely, and David Silva is likely to be one of those.
The Spaniard was City's most influential player for much of last season but, like several of his team-mates, he has struggled to find the same form this campaign.
Mancini conceded Spain's international demands will not have helped, with Silva playing a key role in their Euro 2012 victory, while this season he has already made trips to Puerto Rico and Georgia.
"It is difficult for him," said the City boss. "He's human and probably he's not 100%. I don't think he needs a rest but he played the European Championships and afterwards he travelled twice away, once to Puerto Rico, so for this reason he could be not fresh."
Mancini is also trying to bed in his new signings, particularly Javi Garcia, Maicon and Matija Nastasic, who all arrived from other European leagues on the final day of the transfer window.
Defensive midfielder Garcia was a big-money signing from Benfica, and Mancini added: "Javi Garcia, Maicon and Nastasic all need time. Benfica has a top squad, they win every game. Here it's tough, every game is difficult."
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