The English top-flight champions, with striker Sergio Aguero in outstanding form, should in theory be too strong for their Russian counterparts at the Etihad Stadium, a year to the day since City won the corresponding fixture 5-2.
               
The omens are on the side of the home team too. CSKA have never won in England in five appearances while Aguero has scored seven goals against Russian clubs in four outings for City and previous club Atletico Madrid.
               
However, City's performances in Europe this season have produced two draws and a defeat from three Group E matches and they are now battling to stay in the competition.
               
The second of those draws came in Moscow two weeks ago when they let a 2-0 lead slip in the closing stages, allowing CSKA to recover for a 2-2 draw, but they have no margin for errors now.
               
Bayern Munich lead the way with nine points followed by AS Roma on four, City on two and CSKA on one. Anything less than a home win will put a huge dent in the home team's hopes of advancing to the last 16.
               
A CSKA victory would put the Russians back in the hunt if Bayern, who handed City a lifeline when they thrashed Roma 7-1 two weeks ago, beat the Italian outfit again on Wednesday.
               
Despite a surprise recent defeat by West Ham United, City are third in the Premier League, six points behind leaders Chelsea, and their form domestically is far superior to their results in Europe.
 
Midfielders David Silva and Frank Lampard are sidelined against CSKA through injury while Aleksandar Kolarov is a doubt after being hurt in the warm-up against United on Sunday.
               
While City are showing somewhat schizophrenic form in the two biggest competitions they play in, CSKA travel to Manchester seeking to salvage a season that is beginning to slide.
               
The Moscow side trail leaders Zenit St Petersburg by seven points in the Russian top-flight after losing 1-0 to Andre Villas-Boas' side at the weekend.
               
Javi Garcia, who used to play for City, scored Zenit's winner at CSKA on Saturday.
               
Injuries and suspensions have hit CSKA hard in Europe this season but coach Leonid Slutsky welcomes back Alan Dzagoev and Pontus Wernbloom on Wednesday after both served three-match bans.
               
The Russians will still be without young forward Kirill Panchenko and Swedish midfielder Rasmus Elm who has yet to feature this season because of a serious stomach problem.
               
"We are treating Elm in Sweden and in Russia," said club president Evgeny Giner.

"I was told that 10 footballers in the world suffer from this condition and nine aren't playing football,” he added.
               
"If Rasmus is allowed to play the minimum he is risking is to become an invalid...the maximum risk is he could die,” he further said.
               
Seydou Doumbia, who scored a second-half goal and earned the penalty that Bebras Natcho converted in the 2-2 draw with City two weeks ago, is still looking to get back to full fitness.
               
The Ivorian has been restricted to appearances as an impact substitute recently as he tries to overcome injury problems.
               
"His ankle is still not allowing him to play to the best of his ability," said Slutsky.

"Seydou did not even train with the main squad during the past week,” he added.

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