The Spanish second seed, who appeared to be back to his awe-inspiring best on clay in Rome earlier this month after an unfortunate slip-up on the Madrid blue surface, could face Briton Andy Murray in the semi-finals.
The defending champion will need, however, to keep up his guard in a first-round encounter with Italian Simone Bolelli before a likely match against claycourt specialist Juan Monaco of Argentina in the third round.
Sixth seed David Ferrer of Spain also lies in Nadal's lower half of the draw, as does compatriot Nicolas Almagro, the 12th s eed.
Djokovic, looking to become the first man in 43 years to hold all four grand-slam titles concurrently, faces a possible tricky fourth round against Spain's Fernando Verdasco, while local favorite Jo-Wilfried Tsonga, the fifth seed, would be around the corner in the quarter-finals.
Djokovic, who was defeated by Nadal in the Rome final in straight sets, will start his campaign against Italy's Potito Starace.
Federer, the third seed, could take on David Nalbandian, twice a semi-finalist at Roland Garros, in the second round as the injury-plagued Argentine has dropped to 40th in the ATP rankings.
Federer, who reached last year's final after an epic semi-final clash with Djokovic, starts his quest for a 17th grand-slam title against German Tobias Kamke.
In the women's draw, the Roland Garros c rowd could be treated to a quarter-final tie between second seed Maria Sharapova and fifth-seeded Serena Williams.
Defending champion Li Na, seeded seventh, is in the same half of the draw and takes on Romania's Sorana Cirstea in the first round.
In the upper part of the draw, world number one Victoria Azarenka of Belarus faces a possible quarter-final meeting with 2010 runner-up Samantha Stosur.
A second-round clash between the unseeded Venus Williams and third-seeded Pole Agnieszka Radwanska is on the cards in that half of the draw.
The French Open starts on Sunday.
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