Having clinched a famous victory over Paris Saint-Germain on Sunday, Lyon find themselves 14 points clear of Nantes in the Ligue 1 table, although both sides have struggled for consistency this season.
Match preview
Nantes head into Wednesday's clash on the back of a 3-0 home defeat to Reims, as Will Still's boys claimed another statement victory to continue their remarkable rise in the French top flight.
As a result, the Canaries have failed to win any of their last six Ligue 1 encounters, with a run of two draws and four losses leaving the club four points above the relegation zone with nine games remaining.
It is also worth noting that Nantes have managed to win just one of their previous nine matches across all competitions, booking their place in the semi-finals of the Coupe de France with a 2-1 victory over Lens back on March 1.
Antoine Kombouare's men kicked off their Coupe de France campaign with a 2-0 win against lower-league side AF Virois before claiming penalty shootout victories over ES Thaon and Angers to reach the last eight.
After reaching a ninth Coupe de France final last term - securing their fourth title with a 1-0 win against Nice - Nantes will be hopeful of going all the way once again.
As for Lyon, they have won the Coupe de France on five occasions over the years, although their last triumph came back in 2012 when they defeated semi-professional third-tier outfit Quevilly in the final.
Having notched an impressive 1-0 victory at Paris Saint-Germain on Sunday - courtesy of Bradley Barcola's second-half strike - Les Gones will be confident of reaching their first Coupe de France final in over a decade.
Lyon extended their unbeaten run to six games thanks to the triumph in Paris, with three wins and three draws coming since their last loss, giving the club a fighting chance of clinching European football for next season.
Better still, Laurent Blanc's men have lost just one of their last 13 matches across all competitions, picking up seven wins and five draws along the way.
With second-tier side Annecy facing Ligue 1 strugglers Toulouse in the other semi-final, Lyon have the ideal chance to end their trophy drought this year, as the winner of Wednesday's clash will enter the final as favourites.
Nantes Coupe de France form:
W
W
W
Nantes form (all competitions):
L
W
L
D
D
L
Lyon Coupe de France form:
W
W
W
Lyon form (all competitions):
W
W
D
D
D
W
Team News
Jaouen Hadjam missed Sunday's defeat to Reims after Nantes manager Antoine Kombouare decided to leave the left-back out of the squad as he continues his Ramadan fast.
With fellow left-backs Charles Traore and Quentin Merlin out injured, Sebastien Corchia looks set to continue on the left side of defence, while Joao Victor will occupy the right-back role.
Ludovic Blas and Mostafa Mohamed have both bagged nine goals and five assists in all competitions this season, with the latter expected to replace Andy Delort in Wednesday's starting XI.
Lyon have reported no fresh injury problems ahead of the trip to Nantes, although Chelsea loanee Malo Gusto remains sidelined due to a hamstring issue.
Bradley Barcola could come into OL's starting XI after scoring the winner against PSG last time out, as the 20-year-old has racked up three goals and two assists in his last five Ligue 1 appearances.
Having netted 21 goals in 29 matches this term - including four goals in five Coupe de France outings - former Arsenal forward Alexandre Lacazette will continue to lead the line for Lyon.
Nantes possible starting lineup:
Lafont; Victor, Girotto, Pallois, Corchia; Chirivella; Blas, Sissoko, Mollet, Simon; Delort
Lyon possible starting lineup:
Lopes; Diomande, Lovren, Lukeba; Kumbedia, Lepenant, Mendes, Tagliafico; Cherki, Barcola; Lacazette
Slovakia 
Romania 
Ukraine 
Belgium 
Czech Republic 
Turkey 
Georgia 
Portugal 
Switzerland 
Italy 
Germany 
Denmark 
England 
Spain 
France 
Austria 
AZ Alkmaar 
FC Nordsjaelland 
Monaco 
Servette FC 
Dordrecht 
Feyenoord