United are preparing to face the Stamford Bridge outfit knowing defeat will knock them off the top of the Barclays Premier League and pitch them into a two-game goal difference shoot-out to decide the championship.
Prepared for drama: Ferguson knows the next few days are make or break
It is a scenario Sir Alex Ferguson had hoped to avoid by claiming something from last weekend's trip to Arsenal.
But defeat, plus the memory of how United suffered at Chelsea's hands right in the middle of two huge tussles with Bayern Munich, has led Ferguson to no other conclusion than he must make changes for tomorrow's semi-final second leg with Schalke.
'If you look at our experience of last year, the team were very tired against Chelsea in that next game after losing in Munich,' he said.
'All four semi-finalists lost this weekend too and there are certain statistics that tell you the European games do take it out of you.
'That has to have a bearing on my team selection.
Just champion: Ryan Giggs grabbed the vital first goal that put Schalke on the back foot
'We have two massive games. Both as important as the other.
'Chelsea is massive, so I have to pick the right team tomorrow to ensure I have the same kind of freshness I need for Sunday's match.
'Hopefully I will have the nucleus of a team that is still good enough to win the match.'
Ferguson knows that is not entirely necessary either.
Last week's two-goal victory in Germany means Schalke must come up with a repeat of their destruction of holders Inter Milan at the San Siro.
It appears highly unlikely, even if Ferguson is refusing to take anything for granted.
'It is always dangerous in football to assume you have cracked it; that you have found a sliver bullet or discovered some secret formula for success,' said Ferguson.
Injury worry: Wayne Rooney, who scored in the first leg in Schalke, may be rested
'We live in exciting times for Manchester United and while I want both players and supporters to enjoy every minute of it, we must take nothing for granted.
'It is very easy to get complacent in modern life. There are many examples of it.
'But Manchester United don't regard it as a formality tomorrow and it certainly will not be.'
There are a couple of issues that are steering Ferguson towards his final selection.
Wayne Rooney reported for training on Tuesday morning with a tight hamstring. His importance to United at present is such that Ferguson will not take any risks ahead of the Chelsea confrontation, so the England striker will probably be on the bench at best.
Entering the fray: Fabio Da Silva looks a ready replacement for Rooney
Fabio missed training on Tuesday, so his right-back berth will go to either twin brother Rafael or John O'Shea, whilst the extent of Darren Fletcher's recovery from a virus that has kept him out for over two months will be tested at some point.
'Darren will play part of the game,' declared Ferguson. 'He has shown great improvement from the reserve game last week and his weight is back to normal.
'It is just that issue of game time and a little bit more strengthening.'
As United have recorded eight wins and three draws from their 11 European engagements this term, when Ferguson has repeatedly changed his team around, there is no hint of trouble.
Indeed, it could be argued the Red Devils have performed to a more consistent level in the Champions League than they have managed in domestic combat this term, even though they are still top of the table.
In contention: Darren Fletcher is set to see some playing time, according to Ferguson
'The mundane football of the Premier League is almost incessant tribalism,' said Ferguson.
'You are either playing a London team or a Yorkshire team or a Liverpool team. It creates that incredible competitive edge.
'You go into Europe and it is a different type of football. It is a different way of playing. Different tactics.
'It possibly brings a better concentration from us. It is the only answer I can think of.'
Danger men: United won't relish facing Chelsea duo Fernando Torres (right) and Frank Lampard
Should Schalke be disposed of, United can then look ahead to Chelsea, probably with a degree of trepidation but with Ferguson still viewing the overall picture in a rather straightforward manner.
'We have to be favourites for the title, if only because we are three points ahead,' he said.
'But that can evaporate quite quickly and we have a big job to do.
'As I said last week, the drama is not finished.'
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