Seven points ahead in the French league and top of Group F without a goal conceded, Lyon can make virtually sure of reaching the last 16 by beating Olympiakos on Wednesday.
If Lyon makes it a maximum nine points from three games and Real Madrid and Rosenborg draw, the French club will be five points ahead with three games to go.
English Premier League leader Chelsea, which has won its first nine domestic matches, hopes to move a step closer the second round by beating Real Betis at home. In the same Group G, defending champion Liverpool visits Anderlecht.
Neighbors Inter and AC Milan also top their groups. Inter goes to FC Porto, which won the title two seasons ago, and Milan hosts PSV Eindhoven in a repeat of last season's semifinal.
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