Valencia's 11-match unbeaten run at home in Europe shows the scale of the task facing United, who need at least a point after their disappointing 0-0 draw against Rangers at Old Trafford in their Group C opener.
United have won just once away against Spanish opposition in more than 50 years of European football and Fergie said: "It's obviously the hardest place for us to go. Spain has produced cup-winning teams for years and years and you have to recognise that.
"The standard of Spanish football always been very good, so this is a tough game for us. We're all aware of that.
"But that's the great thing about the European Cup, going to face the best teams in Spain and Italy. That's what makes it such a fantastic tournament."