Marcelo Bielsa's Marseille can cut the gap to Hubert Fournier's men to just one point with victory in front of what is sure to be a boisterous Stade Velodrome crowd on Sunday.
Marseille got back on track after four Ligue 1 games without a win by hammering Toulouse 6-1 away last Friday, and Lyon went close to equalling that resounding scoreline two days later as they won 5-1 at Montpellier.
Yoann Gourcuff scored the only goal of the game in Lyon's 1-0 victory in the reverse fixture back in October, but Fournier will be without the 28-year-old this time around after he suffered a thigh injury at Stade de la Mosson.
Two players who will feature, though, are Ligue 1's two leading goalscorers.
Lyon's Alexandre Lacazette scored twice in the Montpellier rout to take his total to 23 goals in just 25 league games this season, while Marseille's Andre-Pierre Gignac has 16 goals to his name after he rounded off the scoring at Toulouse.
Hoping for a draw in the weekend's headline fixture are second-placed Paris Saint-Germain, who are lurking just a point adrift of Lyon.
PSG boss Laurent Blanc will have to ensure there is no hangover from their dramatic progression in the UEFA Champions League at the expense of Chelsea in midweek as they visit sixth-placed Bordeaux just four hours before Marseille and Lyon clash.
A win for PSG, coupled with a draw or Marseille victory at the Velodrome, would take the reigning champions top of the table for the first time this season.
In a match that is, in its own way, equally as important as Lyon's trip to Marseille, 18th and 19th meet on Saturday when Toulouse visit Lens.
Fourth-placed Monaco, meanwhile, could welcome defender Ricardo Carvalho back for their home game with Bastia on Friday.
Leonardo Jardim's team are one of Ligue 1's form teams, with a run of just one loss in their last 12 games putting them in contention for Champions League qualification.
Also pushing for a top-four berth are Saint-Etienne, and Christophe Galtier's side should pick up three points this weekend at bottom-placed Metz - who are without a Ligue 1 win since November 1.
Other games this weekend see Lille clashing with Rennes, Nice hosting Guingamp, Lorient entertaining Caen, Reims visiting Montpellier and Nantes take on Evian.
