Franck Beria and Marvin Martin have been ruled out of Lille's Coupe de France last-16 tie with Caen at Stade Pierre-Mauroy on Tuesday night due to injury.
Defender Beria is nursing a shoulder problem and 26-year-old France midfielder Martin is suffering with a knee injury as Rene Girard's Ligue 1 high flyers take on Caen in the third of three cup matches taking place on Tuesday.
Girard could also be without Simon Kjaer (teeth) and Pape Souare, who are both listed doubtful for the clash to reach the quarter-finals as Lille take on the Ligue 2 side, who have just lost one of their last five matches.
The Great Danes go into the match on the back of Saturday's 2-0 victory over Sochaux, and Girard told www.lequipe.fr: "Simon is not fully recovered following surgery on his wisdom teeth.
"Pope is feeling a little pain in a tendon and therefore we will not take any risks."
Caen boss Patrice Garande will be without suspended midfield duo Aurelien Montaroup and Jose Saez, who are serving a one-match ban each.
Elsewhere, Montpellier travel to Championnat de France amateur club Cannes in Tuesday's early match.
Also on Tuesday, an all Ligue 2 tie between Angers SCO and CA Bastia will see at least one club from outside the top flight progress into the last eight.
Monaco travel to Nice - in Wednesday night's all Ligue 1 clash - on the back of a great run of form, recording just two defeats in their last 12 matches in all competitions which has seen them claim second in the table.
Claudio Ranieri's side head into the match on the back of Saturday's 2-2 draw at Lorient, while Nice, who knocked out Marseille in the previous round, will be looking to bounce back from a 2-1 defeat to Valenciennes when the two sides clash at the Allianz Riviera.
Rennes travel to Ligue 2 Auxerre hoping to build on Saturday's win at Guingamp after a previous mix of results, while Championnat de France amateur 2 outfit L'lle-Rousse take on Ligue 1 Guingamp, who are in much need of a win after failing to record a victory since they knocked out Concarneau in the last-32 in January.
In Thursday's clash, Remi Garde's Lyon take on to Lens as they bid to build on a great run after suffering just one defeat in their last nine matches in all competitions.