Lyon hold a one-goal lead over Valencia in Gary Neville's first match in charge of the Spanish club.
Valencia had the first chance of the game in the ninth minute but Shkodran Mustafi's header went wide of the target from a corner.
Mustafi put the ball in the net with another header two minutes later, but Aymen Abdennour was adjudged to have committed a foul and the goal was disallowed.
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Maxwel Cornet nearly gave Lyon the lead shortly after when he was played in one on one, but the outstretched leg of Jaume Domenech denied the young striker.
Valencia's poor defensive performance encouraged Lyon to attack and Domenech was called into action twice in succession. First, he palmed out a shot from Sergi Darder before Corentin Tolisso's shot was parried behind.
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Cornet gave Lyon the lead in the 37th minute when he cut into the box from the right wing before curling the ball into the top corner of the net.
Valencia had a penalty appeal turned down shortly before half time.
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