City, who face United in the FA Cup third round on Sunday, are engaged in a three-way fight for the league title with their local rivals and Tottenham.
While City will be without influential Ivory Coast midfielder Yaya Toure and his brother Kolo for up to a month, United and Spurs have no absentees for the 16-team Nations Cup that kicks off on 21 January.
The Toures meet up with the rest of the Ivorian squad in Paris on Saturday before leaving for a two-week training camp in Abu Dhabi.
The brothers miss both legs of the League Cup semi-final against Liverpool plus the Premier League match at home to Tottenham on 22 January.
In total the City pair could miss five league matches depending on the Ivory Coast's progress at the tournament.
"We could have a big problem," said manager Roberto Mancini after City failed in a bid to delay the duo's departure until after Sunday's match. "We play big games without Yaya.
"This month we are losing two players. If we lose another then we will need more players."
There was little sympathy for City's plight from United manager Alex Ferguson.
"All the teams who have African players have never really suffered much," said Ferguson. "If you check the records the teams all seem to sail through it.
"I don't think it makes a great impact when you have a squad of players. There are plenty to occupy those positions until they come back."
While the impact of the Nations Cup in Gabon and Equatorial Guinea has been reduced by the failure to qualify of Nigeria, Algeria and Cameroon, it will be keenly felt in London where Arsenal and Chelsea are set to be deprived of key players.
Chelsea lose strikers Didier Drogba and Salomon Kalou (Ivory Coast) and Arsenal will be without forwards Gervinho (Ivory Coast) and Marouane Chamakh (Morocco).
Newcastle United, who are seventh in the league, are perhaps the biggest losers at the hands of the tournament.
They will be deprived of striker Demba Ba (Senegal), who is second in the league scoring charts this season with 15 goals, as well as powerful midfielder Cheick Tiote (Ivory Coast).
"If it was for half a season I would be disappointed but it's six or seven games and we can deal with that," Newcastle manager Alan Pardew said.
At the other end of the table Queens Park Rangers will lose defender Armand Traore (Senegal) and midfielder Adel Taarabt (Morocco) while Wigan Athletic are without Mohamed Diame (Senegal).
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