Laurent Blanc's side currently occupy ninth position in Ligue 1, nine points adrift of the final European qualification position, while Brest are only three points above the relegation zone.
Match preview
French powerhouses Lyon have struggled throughout the current league season, having suffered the same number of defeats - eight - as victories.
Blanc's side missed out on their accustomed seasonal continental commitments following their eighth-placed finish in the 2021-22 Ligue 1 campaign but will need to improve further between now and June if they want to take their place within a UEFA-organised tournament once again.
Lyon have been successful in five of their 10 league home encounters, accumulating 17 points from a possible 30 on offer, however, the hosts have not been victorious at the Groupama Stadium since a 1-0 victory over Lille at the end of October.
Les Gones were on the wrong end of a surprise defeat to relegation-threatened Strasbourg in front of their less-than-impressed supporters on January 14 but restored some confidence in the dressing room a week later after progressing to the last 16 of the French Cup with a 3-0 success over Chambery.
Redirecting their attention back to Ligue 1, Blanc's side registered a much-needed three points on Sunday against AC Ajaccio courtesy of goals from Johann Lepenant and top scorer Alexandre Lacazette.
Sitting precariously above the bottom four, Brest have only been victorious in four matches throughout the current campaign.
Eric Roy's side have nonetheless shown signs of improvement in recent weeks, putting together a hat-trick of unbeaten league matches that included a notable share of the spoils with 2020-21 Ligue 1 victors Lille on January 11.
Victorious in only two of their league matches on the road, Les Pirates began their proposed excursion away from the relegation zone in less-than-ideal circumstances by being knocked out of the French Cup by high-flying Lens last weekend.
Nonetheless, Brest bounced back to form with a comprehensive 4-0 victory over fellow relegation candidates Angers at the Stade Francis-Le Ble on Sunday, courtesy of strikes from Jeremy Le Douaron, Steve Mounie, Franck Honorat and Pierre Lees-Melou.
Lyon Ligue 1 form:
D
W
L
D
L
W
Lyon form (all competitions):
W
L
D
L
W
W
Brest Ligue 1 form:
W
L
L
D
D
W
Brest form (all competitions):
L
L
D
D
L
W
Team News
Clermont manager Eric Roy will again put his faith in former Huddersfield Town striker Mounie to spearhead the visitors' attacking threat at the Parc Olympique Lyonnais.
After scoring on Sunday, Le Douaron, Lees-Melou and Honorat will start alongside Hugo Magnetti and Mahdi Camara in an attack-minded Les Pirates' set-up.
Already showcasing an enterprising run in front of goal across the current Ligue 1 campaign, veteran Lyon forward Alexandre Lacazette - 12 league goals and four assists - will again lead the Les Gones' line on Wednesday evening.
Following on from opening his goalscoring account for the current season, highly sought-after defensive midfielder Johann Lepenant will once more be one of the first names on Laurent Blanc's starting team sheet.
With a clean sheet in their back pockets against Ajaccio, Sael Kumbedi, Sinaly Diomande, Dejan Lovren and Nicolas Tagliafico will open the contest as goalkeeper Anthony Lopes's last line of defence.
Lyon possible starting lineup:
Lopes; Kumbedi, Lovren, Diomande, Tagliafico; Lepenant, Cherki, Barcola, Tolisso, Caqueret; Lacazette
Brest possible starting lineup:
Bizot; Fadiga, Chardonnet, Herelle, Brassier; Lees-Melou, Honorat, Camara, Magnetti, Le Douaron; Mounie