Lyon forward Aldo Kalulu faces another lay-off after he suffered a thigh injury in the warm-up of Saturday's victory against Angers.
Kalulu, who missed more than two months with a serious ankle sprain suffered in October, was forced to sit the game out and Mathieu Valbuena took his place in the starting line-up for the 3-0 win at Stade Jean-Bouin.
And scans have shown Kalulu suffered a partial detachment of the adductor muscle.
Coach Bruno Genesio told the club's website: "It's difficult to predict how long Aldo will be out."
The 20-year-old at least has the consolation of having signed a new long-term contract at the club on Monday, along with fellow academy graduate Mouctar Diakhaby. The pair committed their futures to the club until June 2019.
Nabil Fekir, Rafael and Gueida Fofana will also miss Wednesday's Coupe de France last-16 clash with Paris Saint-Germain.
Lyon were knocked out of the Coupe de la Ligue by PSG in January and lost 5-1 to them in Ligue 1 in December.
Laurent Blanc's side lead the league standings by 24 points after Sunday's win over Marseille as they march towards a fourth straight title.
Genesio said: "I think we are capable of winning tomorrow but it also depends on PSG's level. If PSG are at their top level, they are unbeatable in France.
"They are the best team I've ever seen in France. I am not jealous of PSG, it's good for French football.
"Maybe they could be preoccupied by the Champions League and they will also have Sunday's match in their legs, we have an extra day's rest."