Separated by six points in the Ligue 1 table, ninth-placed Lyon and sixth-placed Lille will be desperate to progress in the cup, as both teams find themselves off the pace in the top-flight title race.
Match preview
Following a disappointing 2021-22 campaign, Lyon are on course to record back-to-back mid-table finishes in Ligue 1, having endured a difficult season up to now.
Peter Bosz was sacked in October after overseeing four straight league defeats, with Laurent Blanc coming in as his successor, but the 57-year-old has struggled to steady the ship.
OL have registered five wins, three draws and four losses in the league since Blanc's appointment, highlighting their struggle for consistency, although they head into Wednesday's clash on a run of one defeat in seven outings across all competitions.
Thanks to goals from Bradley Barcola, Rayan Cherki and Alexandre Lacazette, Lyon beat Troyes 3-1 on Saturday, meaning Barcola and Lacazette have dished up nine goal involvements between them since the turn of the year.
Blanc's men kicked off their Coupe de France campaign with a 2-1 victory over Metz before defeating Chambery 3-0 in the previous round, so they will be hopeful of maintaining their recent upturn on home soil.
Lille, on the other hand, come into Wednesday's clash on a run of one defeat in 11 matches across all competitions, having claimed six wins and four draws since losing 1-0 to Lyon in Ligue 1 back in October.
Paulo Fonseca's side extended their hot streak with a 3-1 victory over Rennes last time out, recovering Amine Gouiri's first-minute strike to score three second-half goals, with Edon Zhegrova, Remy Cabella and Andre Gomes finding the net.
Not only have Lille lost just one of their last nine Ligue 1 matches, but they have also lost two of their previous 13, keeping themselves within touching distance of the European places.
LOSC clinched comfortable 2-0 wins against Troyes and Pau to reach the last 16 of the Coupe de France, although they are unlikely to enjoy a similar level of dominance against a resurgent Lyon outfit.
It is worth noting that Lille have reached a solitary Coupe de France final since 1955, lifting the trophy in 2011, while Lyon triumphed in 2012, securing the silverware for the second time in five seasons.
Lyon Coupe de France form:
Lyon form (all competitions):
D
L
W
W
D
W
Lille Coupe de France form:
Lille form (all competitions):
D
W
W
L
D
W
Team News
Blanc could hand starts to Houssem Aouar and Henrique on Wednesday, as both players have returned to first-team action following injury, although they may have to settle for a place on the bench.
Alexandre Lacazette has scored three goals in two Coupe de France appearances this season, in addition to 13 goals in 22 league outings, so the ex-Arsenal forward will be confident of enhancing his tally in the cup.
Lille will be without injured forward Gabriel Gudmundsson for the trip to Lyon, while midfielder Adam Ounas is also expected to be absent after missing the last four games.
Having bagged 13 goals and four assists across all competitions this term, Jonathan David will lead the line for the visitors, with Angel Gomes and Jonathan Bamba supporting the club's top scorer.
Lyon possible starting lineup:
Lopez; Gusto, Diomande, Lovren, Lukeba; Lepenant, Tolisso, Caqueret; Cherki; Barcola, Lacazette
Lille possible starting lineup:
Chevalier; Diakhite, Yoro, Djalo, Ismaily; Andre, Gomes; Zhegrova, Gomes, Bamba; David