City's 1-0 defeat at Swansea on March 11 saw Roberto Mancini's men lose top spot in the table for the first time since October.
Local rivals Manchester United's 5-0 thumping of Wolves on Sunday means City will kick-off against a revived Chelsea four points behind the champions.
United have a simpler run ahead of their trip across town to Eastlands in the third-last game and City supporters acknowledge another slip at this stage could potentially kill off their hopes of a first title since 1968.
Mancini could call on Carlos Tevez for the first time since September after the Argentina forward returned from three months of self-imposed exile in his homeland.
The striker has made two appearances for the reserves and could feature against Chelsea, almost six months since falling out with Mancini after refusing to come off the bench against Bayern Munich.
City defender Joleon Lescott insisted the squad would have no problems welcoming back Tevez into first-team action.
"He's like a new signing. He's not been injured so he is not going to be struggling too much in terms of sharpness and fitness," Lescott said.
"All the boys are excited and can't wait for him to get playing again," the England international added.
"Over the last two years he has probably performed at the highest consistent level as anyone else, so none of us discourage what Carlos has done for the club and obviously what he continues to do."
Roberto di Matteo takes his fifth-placed Chelsea side to Eastlands in search of a fifth straight win since taking over from the sacked Andre Villas-Boas.
Two of those wins have been in the FA Cup against opposition from the Championship, with Birmingham and then Leicester City eliminated from the knock-out competition.
But the 4-1 Stamford Bridge success in the Champions League against Napoli, which overturned a 3-1 first leg deficit in extra time, has already gone down in history as one of the club's greatest nights.
In addition, Fernando Torres scored twice in Chelsea's 5-2 win over Leicester City on Sunday to end a goal drought of five months.
"Fernando has been doing really well but he was just unlucky not to be scoring," Chelsea goalkeeper Petr Cech said. "He has had a lot of assists, has been working hard for the team and it was great to see him get his reward.
"He must be delighted because as a striker you think of goals and on Sunday he scored twice and that is great for his confidence."
Cech is convinced Chelsea can take advantage of City's poor recent form.
"They have a great squad, full of internationals and great players," he said.
"They had a good start to the season and after a few bad results things are looking different.
"But there is still a long way to go. If they get three points from Wednesday then they will still have a chance to win the League, but obviously we want to stop this happening."
John Terry, Frank Lampard, David Luiz, Ashley Cole, Michael Essien and Ramires are all set to return to the starting line-up.