The Portugal international - on loan from Sporting Lisbon for the campaign - suffered the injury in Sunday's 1-0 Ligue 1 win over Guingamp, with tests later revealing a fracture to the tibia in his left leg.
The defender will undergo surgery on Tuesday, and will then be forced to wear a cast for the following six weeks as he begins his rehabilitation.
Lopes has made 31 appearances in all competitions for Lyon this season but joins a lengthy injury list that could hamper coach Remi Garde's hopes of securing European football next season.
The likes of Clement Grenier, Samuel Umtiti, Gueida Fofana, Henri Bedimo, Milan Bisevac and Mouhamadou Dabo are also unavailable for selection.
Lopes is set to return to parent club Sporting when his loan deal finishes at the end of the season.
