Lyon were without influential midfielders Juninho and Jeremy Toulalan and talismanic striker Karim Benzema, all of them rested, when they surrendered their trophy in a 3-2 defeat in the last-16 at Lille on Wednesday night.
The trio will return at the Stade de France as the leaders look to extend their unbeaten streak in Ligue 1 to 10 matches and defend a four-point lead (53 points from 26 games).
"It was quite hard to concede that goal in stoppage time but that's football. We must put this game behind us and focus on Saturday's game against the same team," Lyon midfielder Jean Makoun told the club's website.
Lyon coach Claude Puel may have to do without Ghana defender John Mensah, who picked up a muscle injury on Wednesday.
"Both teams played the same match with the same effort. I hope Saturday's game will be as pleasing to watch, with a different result at the end," said Puel.
HOME FORM
Although he might want to add fresh blood to his squad, Lille coach Rudi Garcia could be tempted to field 18-year-old Belgian striker Eden Hazard, who scored one and set up the other two in a man-of-the-match performance on Wednesday.
Second-placed Paris St Germain could reduce Lyon's lead to one point should they win at Lorient and the leaders lose.
PSG, upset by third division Rodez in their French Cup last-16 match, will have to cope with the absence of midfielders Claude Makelele and Stephane Sessegnon, who started two-match and three-match suspensions respectively on Monday.
Third-placed Olympique Marseille, one point further back, host Valenciennes looking to improve on their mediocre home form. They have won half their 48 points on the road.
"Twenty-four points away from home is a good performance but we definitely should have more from our home games," Marseille defender Laurent Bonnart told the club's website.
Saturday's crunch match features fourth-placed Girondins Bordeaux away to fifth-placed Toulouse, with the team that loses virtually out of the title race.
Bordeaux, who have 47 points, are six adrift of Lyon with Toulouse one point further back.
