The Liga side need three points to put themselves in contention for a place in the knockout stages,as well as hoping that Gent fail to beat Zenit in the other game in Group H.
Negredo recently returned to training following two months out with a knee injury, while reports also suggested the striker had fallen out with former coach Nuno Espirito Santo.
Speaking at his pre-match media conference, Neville insisted that the striker will be not be rushed back into action but hinted that he may feature on Wednesday.
"He's not played for two months but he is in the squad for tomorrow evening and we'll need to build up his match sharpness because he's been out a long time," Neville said.
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"The thing with Alvaro is to bring him back in little by little because he hasn't done that much training.
"It has to be our own pace, that suits Alvaro and the doctors and fitness coaches, but there is the chance for us to play with two strikers at some point [against Lyon].
There has been suggestion that the language barrier will be difficult for Neville to overcome during his first managerial role.
The former Manchester United and England defender admitted that he will take a while to get up to speed but, with brother Phil and FA video technician David Scoulding part of his backroom staff, he does not feel it will have a negative impact on his job.
"Some of the players speak English and I am learning some of the key phrases in Spanish but I have a long way to go," the England coach added.
"Because of Phil, because of David and some players speaking English it has been easier.
"Because I can demonstrate things visually on the pitch and on video then they understand straight away because players understand football."