Marcelo Bielsa's league leaders are in red-hot form, coming into the cup contest off eight straight wins in the French top flight.
Marseille claimed a league cup hat-trick from 2010 to 2012, but no silverware has landed at the Stade Velodrome since.
The two clubs have endured a close rivalry in recent times, Marseille's 3-0 Ligue 1 win at home to Rennes in September snapping a three-match winless run against the north-west club.
Rennes won their only other clash against Marseille this year, claiming a 1-0 triumph away from home in March.
Marseille will be hoping to preserve their winning streak, despite having to travel on one of the longest trips in French football.
An out-of-form Bordeaux are up against an equally out-of-sorts Toulouse for a spot in the last 16.
Willy Sagnol's Bordeaux are winless in three, while Toulouse have failed to trouble the scorers in two straight league losses.
Their past two meetings in Ligue 1 have featured three red cards, meaning there could be some spite on show at Toulouse's Municipal Stadium.
Also on Tuesday, Evian and Lorient do battle in an all-Ligue 1 contest - both sides flirting with relegation early in the domestic campaign.
The remaining six matches on Tuesday feature a top-flight team against a Ligue 2 outfit.
Mid-table Montpellier are at home to second-tier Ajaccio, Reims welcome Ligue 2 strugglers Arles and relegation-placed Bastia welcome an in-form Auxerre side.
Ligue 1's Lens are at home to Creteil, Laval - on the back of four straight draws - will hope to upset Nantes, while top-flight side Caen will host Ligue 2 battlers Clermont.
Also on Wednesday, Nice and Metz - separated by just one point in the Ligue 1 table - will clash at the former's Allianz Riviera.
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