Juventus's shock loss to Young Boys left the door open for United to go through to the last 16 as  group-winner, but a Carlos Soler strike and a Phil Jones own goal saw resulted in a loss at the Mestalla, although Marcus Rashford netted a consolation.

Jose Mourinho made a number of changes to his starting line-up, with the Red Devils' place in the next round secure and a trip to Liverpool looming, and the players on show, including Paul Pogba and Romelu Lukaku, did nothing to suggest they will keep their spots for that game at Anfield.

The result means little to Valencia, which was already assured of a Europa League place, but the ease with which it claimed only a second competitive win over United will give it heart amid a difficult season.

Valencia went ahead with the first shot on target of the match, Soler drilling clinically into the bottom-left corner of Sergio Romero's goal after Jones had headed a cross straight to him.

Juan Mata had United's first effort of the game 26 minutes in and was unlucky not to win a penalty, with Mouctar Diakhaby clearly blocking the goal-bound shot with his arm, before Paul Pogba somehow prodded wide with the goal at his mercy after a corner.

With no shots on target before the break, United would have hoped for a strong start to the second half, but it was 2-0 down 47 minutes in when Jones diverted a throughball past the onrushing Romero.

Substitute Rashford finally tested Valencia goalkeeper Jaume Domenech 72 minutes in, and Andreas Pereira was unlucky to see a stinging effort clawed away by his former team-mate, as United at last put the home side under pressure.

Rashford met Ashley Young's cross with a firm header with three minutes of normal time left, but Juan Mata failed to connect with a clever Pogba chip as the chance to rescue a draw came and went.