The visitors, who have six points to their name, will be looking for a response after losing 2-1 to Lorient at the weekend.
Match preview
Igor Tudor will be pleased with his start as Marseille boss after overseeing three wins and a draw in his club's opening four games.
A comfortable win over Rennes was followed by a 1-1 away draw against Brest before they returned to winning ways with a 2-1 victory over Nantes.
They travelled to the Allianz Riviera on Sunday to face a winless Nice side, with an Alexis Sanchez brace and a Nuno Tavares goal wrapping up a 3-0 victory by half time.
Having taken 10 points from their first four matches, second-place Marseille are level on points with Paris Saint-Germain and Lens at the top of Ligue 1.
After scoring twice in three of their opening four encounters, Tudor's side will believe that have the firepower to claim a third consecutive victory on Wednesday.
Meanwhile, Clermont have already lost 5-0 to Paris Saint-Germain this season, so they will be aiming to avoid another heavy defeat against one of the division's top sides.
However, Les Lanciers responded to their opening day loss to PSG in style, beating Reims 5-2 before edging out Nice in a home encounter.
Pascal Gastien's charges were hoping to claim a third straight win on Sunday against Lorient, but a second half strike from Muhammed Saracevic could not prevent Clermont from avoiding a 2-1 defeat.
Having collected six points from their four matches, Clermont currently occupy a respectable ninth place and can move within a point of Marseille if they win on Wednesday.
Ahead of the midweek contest, the visitors will take inspiration from the 2-0 away win they recorded against Marseille in their most recent meeting in February.
Marseille Ligue 1 form:
Clermont Ligue 1 form:
Team News
Eric Bailly came off the bench to make his debut for Marseille at the weekend, and the defender could be given his first start on Wednesday.
Sead Kolasinac could drop out of the side to make way for Bailly in what could be Tudor's only change for the home encounter.
Another new addition Sanchez opened his Marseille account with a brace on Sunday, and the 33-year-old will have the chance to add to his tally when he leads the line against Clermont.
As for the visitors, they are expected to be without the services of Mehdi Zeffane and Elba Rashani due to injury issues.
Neto Borges will serve a one-match suspension after being sent off against Lorient, with the left-back set to be replaced in the starting XI by Arial Mendy.
Yohann Magnin may also be brought into the lineup, while Jeremie Bela could be given his first start for the club after making three substitute appearances.
Marseille possible starting lineup:
Lopez; Bailly, Balerdi, Mbemba; Clauss, Rongier, Veretout, Tavares; Guendouzi, Payet; Sanchez
Clermont possible starting lineup:
Diaw; Seidu, Wieteska, Ogier, Mendy; Gastien, Magnin; Allevinah, Cham, Bela; Andric