Manuel Pellegrini has already guided his side to one cup glory this season but could rest players for Sunday's fixture ahead of Wednesday Champions League clash with Barcelona.
Ben Watson's late header at Wembley earned the Lancashire club a stunning 1-0 victory over City to lift the FA Cup for the first time, although the club was relegated from the Premier League only a matter of days later.
Manuel Pellegrini's side added one trophy to its cabinet last Sunday when it beat Sunderland 3-1 in the Capital One Cup final and can move a step closer to winning another by making it a miserable return to the club for Wigan manager Uwe Rosler.
The German was a big fans' favorite during his playing days at City, scoring 50 goals during a four-year spell at the club in the 1990s.
Rosler, who was named the Championship’s manager of the month for February on Friday, said: "My first reaction [following the draw] was to ban all talk of that game. We started talking about this game this week. It was important to focus on the league.
"We go into the game with no pressure whatsoever. The pressure lies on City. We already achieved a wonderful cup run. Being in the sixth round of the FA Cup has only happened in the third time in the history of the football club.
"And doing that on the back of last year's win made it even more special. We overcame big hurdles and now the hurdle is very big, but that also means there is a great challenge in front of us, for me as a manager, but also for my players to measure yourself against world-class players."
Wigan, which has beaten top-flight sides Cardiff City and Crystal Palace en route to the last eight, has moved into the top six in the second tier on the back of a run of four consecutive victories and has also won its last four away matches in all competitions.
On-loan midfielder Nick Powell (hamstring) is not expected to feature and Watson will play no part as he is a long-term absentee due to a broken leg, but the midfielder was this week awarded a new one-year contract.
Scott Carson (thigh), Gary Caldwell (calf) and Shaun Maloney (hip) are also expected to remain on the sidelines.
Martyn Waghorn, Ryan Tunnicliffe and Rob Kiernan are cup-tied, but Callum McManaman (ankle) could return.
City boss Pellegrini will have one eye on Wednesday's Champions League last-16 clash at Barcelona, when his side has the major task of trying to overturn a 2-0 deficit from the first leg.
The Chilean is expected to make changes, but he will not be able to call upon Stevan Jovetic (hamstring) and Matija Nastasic (knee).