Both sides, who sit in third and fourth respectively, could leapfrog second-place Paris Saint-Germain and leaders Monaco with a victory, though the hosts would need to win by three goals.
Eli Baup's men are one of three sides on 11 points but have not won in their last three games, while Christophe Galtier's charges come into the clash off the back of a surprise 2-1 defeat to Toulouse on Friday.
The visitors won the last fixture between the two in May, the first time they had beaten Marseille in 12 attempts, and Galtier will hope Romain Hamouma can continue his fine form, having scored three times in the league this season.
Monaco host Bastia, who are on a three-match unbeaten run, while PSG, who were held at home by the big-spending table-toppers having won their previous three matches, face struggling Valenciennes.
Lyon picked up their first win in four matches against Nantes on Sunday, thanks to goals from Bafetimbi Gomis, Clement Grenier and Jimmy Briand, and will look to make it two wins in four days against Ajaccio.
Gomis, who had looked set to leave the club in the close-season along with Briand, is now committed to the club and wants to contribute further for Remi Garde's side.
"Jimmy and I have played 500 matches between us in Ligue 1," he is quoted as saying by ESPN. "That counts for something. We bring our experience to the team.
"I've moved on. I'm happy to score for Lyon and my objective is to reach 100 Ligue 1 goals in the shirt of this club."
Nice and Rennes, fifth and sixth respectively, both have away trips, with the former taking on Nantes on Wednesday and the latter facing Montpellier on Thursday.
Bottom side Sochaux will hope to pick up their first victory of the season against a Guingamp side without a win in three games, while Bordeaux, who have taken one point from the last three matches host Reims - a side unbeaten in five.
Eighth-place Lille and mid-table Evian are in action at the Stade Pierre-Mauroy on Tuesday, with the visitors having taken seven points from their last three games following back-to-back consecutive defeats, while Toulouse and Lorient, separated by a point in the table, meet at the Stadium Municipal a day later.
