Philippe Clement's principality outfit are still six points adrift of third-placed Nice, who host Clermont on Sunday, in the race for the Champions League.
Lyon drop to eighth and could be nine points off the top three by the end of the weekend as they look to avoid missing out on Europe's premier competition for a third straight season.
"The Champions League? We can always dream," said Lyon coach Peter Bosz. "But now, we have to win the next match... There is disappointment, anger."
Brazilian Jean Lucas gave the home side a second-minute lead at the Stade Louis II.
France striker Ben Yedder continued his remarkable goalscoring form by firing a shot in off the post before the half-hour mark.