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David Wright and David Connolly are both struggling with hamstring injuries while Emerson Thome is still suffering with a fractured cheekbone.
Steve McMillan is still injured and Ryan Taylor is ruled out with a broken foot.
De Zeeuw has been struggling with an ankle injury and is expected to sit the game out, while Lee McCulloch will definately be missing. The Scotland international has under-gone surgery on a double hernia.
Goalkeeper Mike Pollitt may be rested for the game as he was in the last round. The hero 'keeper said: "I did not play in the last round, so we will just have to wait and see whether I play in this game.
"But it is another competition we want to do well in. If we can keep winning matches, getting through the rounds and staying up there in the league, it will be good for us.
"We are still in the top six of the league, so that also gives us a great chance to get into Europe."
Meanwhile, striker Neil Mellor says his family will have divided loyalties for the game. Mellor's family are Manchester City supporters, but the 23 year old is confident they will change their colours to support him.
He said: "When I was asked to come down to Wigan the first thing I thought about was the semi-final against Arsenal, and then the game with City because all my family are Manchester City fans.
"When I was growing up, and before I went to Liverpool, I was a City fan. I enjoyed some good moments watching them, but after going to Liverpool things changed.
"But this FA Cup game will be a massive game, and one in which I've no idea whether my family will be supporting me or City.
"My dad has obviously played for City, and I think he'd be quite happy if he saw me score and win. For this day alone he'll maybe be a Wigan fan."
Wigan (from): Pollitt, Filan, Walsh, Chimbonda, Baines, Henchoz, Scharner, Jackson, Teale, Mahon, Bullard, Kavanagh, Francis, Johansson, Skoko, Ziegler, Roberts, Mellor, Joyce, Lee.
For Manchester City, Danny Mills and Claudio Reyna are both out with leg and ankle injuries respectively. Right back Sommeill is available again after he has served a three match ban for a horror tackle.
City beat Scunthorpe 3-1 in the third round to progress. Robbie Fowler managed a hat-trick that day for the Laser Blues.
Here is how City lined up that day: James, Onuoha (Croft 45), Dunne, Distin, Jordan, Sinclair, Barton, Jihai, Ireland, Fowler, Sibierski (Wright-Phillips 69).
It is doubtful that boss Stuart Pearce will play such a young side on Saturday with his side facing the Carling Cup finalists.
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