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 defence following his Man of the Match performance in Monday's 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 are 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 equaliser in that match, could replace him in the starting 11.
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.
|DID YOU KNOW?|
- Manchester City have faced Barnsley twice before in the FA Cup (both at home), winning 2-1 in 1947/48 (round three) and 2-0 in 1992/93 (round five).
- This is the first time Barnsley have made it past the third round since the 2007/8 season, when they famously defeated Liverpool and Chelsea to reach the semi-finals.
- Tykes boss David Flitcroft is the brother of former City midfielder Garry, who made 134 appearances for the club between 1992 and 1996.
- The Yorkshire side also have Kelvin Etuhu (pictured, right) in their ranks, who came through the youth system at the Etihad Stadium and scored one goal for the first team before moving on.
- Roberto Mancini’s side are unbeaten in nine games against lower league sides in the FA Cup, winning their last four in a row without conceding a single goal, while scoring 13.
- City have lost four of their last five FA Cup quarter-finals, though they did win their last one in 2011 against Reading on the way to lifting the trophy.
- The hosts' sturdy defence have kept six clean sheets in their last seven home games in all competitions. Manchester City are 11/2 to beat Barnsley 3-0 with bet365.