Already without Gareth Barry through suspension, with Mario Balotelli deemed "unlikely" to recover from an ankle injury sustained in training last week and Samir Nasri trying to shake off an illness, Mancini always knew his resources would be depleted.
So he could have done without the double whammy of losing Yaya and Kolo Toure after his plea to keep the pair until after the United game was rejected by Ivory Coast coach Francois Zahoui.
So, instead of facing Sir Alex Ferguson's men, the Toures will be flying from Paris, where they are required for a team meeting on Saturday, to Abu Dhabi for a two-week training camp ahead of the tournament, jointly held in Gabon and Equatorial Guinea.
And evidently, Mancini has no faith in some of the back-up players outside his senior squad because he is contemplating the possibility of naming only six substitutes.
"For Sunday we have 17 players," he said. "I don't think we will have 18.
"Gareth is suspended, Mario is injured. Samir was better yesterday but I don't know."
The strange case of Owen Hargreaves offers little cause for optimism either as two starts in the Carling Cup and a substitute appearance in the Premier League win over Aston Villa have not given way to a more consistent presence in the City squad.
"Owen has worked with the team in the last two weeks without a problem," said Mancini.
"But it is clear that he is not Yaya at this moment.
"He needs to play and work. I hope he can be ready to play one game but it depends on him."
It leaves Mancini with just James Milner and Nigel de Jong available to face United from his pool of orthodox midfielders, although that could be supplemented by Pablo Zabaleta, or even Nasri should the former Arsenal man recover in time.
"I always said we could have a problem in January," said Mancini.
"Yaya is an important player for us. Kolo is different because we have eight defenders and no injuries.
"It is in midfield where we have a big problem."
It is still hard to believe Mancini won't have a full compliment of players available to him on Sunday, although it does explain why City have repeatedly been linked with Roma's Daniele De Rossi.
In the short term, though, Mancini will make do with what he has, meaning both sides may end up limping into the game given the chronic state of United's fitness over the past month.
A week ago, it seemed the Red Devils would harbour high hopes of avenging that 6-1 nightmare to City at Old Trafford in October.
Since then though, they have lost to Blackburn and Newcastle, where they were comprehensively beaten last night, as opposed to their rivals, who bounced back from that shock loss to Sunderland by romping past Liverpool on Tuesday.
"After two defeats, maybe another one would be a problem," said Mancini.
"But I still think they are very strong.
"I don't remember when I lost three matches in a row.
"Ferguson has won so many trophies but there are some periods when you have difficult times, when players are injured.
"At the moment it is very hard and in football, there are some situations that are very strange.
"But United has one very positive thing. Their mentality is strong.
"After one or two defeats, it is like it didn't happen. They start to play strongly again.
"Like after they lost to us, they won eight games out of nine.
"For this reason they are always very dangerous."