Eyal Berkovic, Paul Bosvelt and Antoine Sibierski, have added to Kevin Keegan's midfield selection worries after impressing for the reserves on Tuesday. Keegan may deploy Nicolas Anelka as a lone striker, allowing an extra midfielder in order to stem the threat from the hosts.
But attacking will be the biggest concern for Keegan after City have failed to score in four league games while United have conceded in just 2 of their last 11.
"Defensively we have been solid, it's scoring goals that has been a problem," admitted Keegan.
"It's a new one for me because if you go back right through my time at Manchester City most people would have said the biggest worry was leaking them at the other end.
"We turned it round at Everton last week, now we have a major test to see if we can get back to where we want to be."
Meanwhile, City fans voted in an M.E.N. poll that Trevor Sinclair should be given a break from the starting line-up after failing to make an impact since his arrival.
Otherwise, Joey Barton and Shaunny Wright should remain in the side in recognition of their consistency and Steve McManaman is a likely starter after a positive return to the line-up at Everton.
Although City go to Old Trafford on the back of a poor run, Keegan believes the Blues can come away with a result.
"Obviously we would have preferred to be playing Manchester United on a run of form," he told the official club site.
"But remember we lost to Wigan before the first derby last season. Form is always a good thing and you would always prefer to be winning but I don’t think our fans should be going to Old Trafford on Saturday with massive amounts of trepidation."
Keegan added: "We have got players who have played there many times, who have scored goals there and have won games there in different teams.
"We have got the ammunition available to be able to go there. We have got the ability to be able to play them and that is what we shall do.
"That is what we did last year when we got four points out of six. That was a terrific achievement as they were the Champions and not many other teams did that.
"But that was last year, now we have to do it again and I am hoping for a big performance from everyone. Make no mistake about it, this is our toughest game of the season and in our fans eyes the biggest of the season and we are aware of that."