With the Premier League title a distant hope, Roberto Mancini is expected to field a strong side in order to keep his team in the hunt for silverware.
Costel Pantilimon should keep his place in goal ahead of the rested Joe Hart, having played in each of the previous three rounds. Captain Vincent Kompany will not be risked as he makes his was back from a calf injury, meaning Kolo Toure should continue alongside Matija Nastasic in defense following his Man of the Match performance in Monday's league win over Aston Villa.
Jack Rodwell (hamstring) is unfit after going off at Villa Park, and Sergio Aguero will also miss out after suffering a knee injury in training.
Barnsley is without left back Scott Golbourne, who suffered a season-ending knee injury in the last round against MK Dons.
The Tykes are expected to revert back to a 4-4-2 formation, with Marlon Harewood dropping to the bench after starting in an adventurous front three against Burnley. Tomasz Cywka, who grabbed the late equalizer in that match, could replace him in the starting XI.
City loanee Ryan Tunnicliffe is ineligible to face his former side, while on-loan Stoke midfielder Rory Delap will compete with former Chelsea youngster Jacob Mellis for a starting spot alongside David Perkins in the middle of the park.
Jason Scotland should continue in his role as 'super sub', with Chris O'Grady expected to partner Chris Dagnall up front.