Los Che go into the game flying high in the La Liga.
"It is going to be a difficult match," said Fletcher. "People might say it is not the same Valencia because they have lost Villa and Silva.
"But as we have seen at Manchester United, when you lose good players others step up to the mark and take on more responsibility. They have had a fantastic start."
United cannot say the same.
"We have picked up experience of playing in Europe and we have confidence," said Fletcher. "We know how to cope with the travel and the different styles of play.
"Against Spanish sides, keeping the ball is key. If you give the ball away cheaply, you might not see it for a few minutes and they will punish you."