Elie Baup's men are still looking for their maiden win in Group F and are up against Rafa Benitez's side which will be hoping to get back to winning ways.
Elie Baup's men failed to take a single point from their opening two Group F games, suffering defeats against Arsenal and Borussia Dortmund respectively.
Napoli is one place ahead of Marseille in the standings after following up a win over Dortmund with a 2-0 loss at Arsenal last time out.
Marseille has won just two of its last six encounters in continental competition.
Both those victories came in the Europa League against weaker opposition, and Rafa Benitez's side - which heads into the clash on the back of its first Serie A defeat of the season against Roma on Friday - will fancy it chances of getting back to winning ways in France.
Gonzalo Higuain is likely to be key to Napoli's hopes, with the Argentina international striker having scored four times for the club since joining from Real Madrid in July - including the opener in a 2-1 success over Dortmund last month.
Still, the club's away record in the Champions League is far from impressive, with Napoli tasting victory in just one of its last five games on its travels.
Marseille should take heart from that statistic, and will hope that striker Andre-Pierre Gignac can produce his best form as the club seeks its first points of the competition.
Gignac scored 18 goals in all competitions last season, but has found the net just three times so far this term.
Meanwhile, Benitez has a near fully-fit squad to choose from, with winger Juan Zuniga the only absentee.
Dimitri Payet is poised to return to the Marseille side after the winger missed Friday's 1-0 defeat to Nice through suspension, providing Baup with a full complement of players.
Marseille's last victory in the Champions League came in 2012 as the club beat Inter in the last 16, and Baup will hope his side can replicate that surprise win as it aims to keep its qualification chances alive.