Manchester City will be without David Silva and Mario Balotelli for tomorrow's crucial Premier League encounter at Arsenal.
The pair have both been struck down by knee injuries, with Silva possibly out for two weeks.
"It is a big problem," said manager Roberto Mancini.
"Neither of them will be available."
Silva in particular will be a huge loss at the Emirates given his growing influence on the Blues in recent weeks.
"David has been an important player for us and has been doing well recently," said Mancini.
"Hopefully, he will be back for the Wolves game on January 15. Mario might be back for the FA Cup tie at Leicester on Sunday."
Mancini also confirmed he is confident of securing the services of Bosnian striker Edin Dzeko from Wolfsburg.
"We have agreed a fee," said the Italian.
"He is a good player and all the teams in Europe want him. But we have an important game at Arsenal coming up and I will speak about him after that."
Meanwhile, Mancini claimed that his side are still outsiders in what he accepts is now a five-team pursuit of the title.
City are joint top with neighbours Manchester United, although they have played two games more.
And Mancini, who has previously claimed that Chelsea would stroll to the championship, feels that City's inexperience in such situations could count against them.
"Arsenal, Chelsea, United and Tottenham all have more experience than us," he said.
"Probably one of those four teams will win the title.
"We just want to work, so we can improve and try to keep getting better."