Fourth seed Nadal, who has only lost one match on clay this season, was handed a tricky first-round opponent in the mercurial Benoit Paire on Friday.
Serbian Djokovic, the second seed, will take on Spain's Marcel Granollers, a man who has won three of his four ATP titles on the red dirt.
World number one Andy Murray, who has been struggling this season, will play Russian Andrey Kuznetsov and faces a potential third-round with either claycourt specialist Nicolas Almagro or Argentine Juan Martin Del Potro.
Third seed Stan Wawrinka of Switzerland, the 2015 champion, will face a qualifier and could meet Murray in the semi-finals.
In the women's draw Czech Petra Kvitova, who has not played competitive tennis since being stabbed during a burglary at her home last December, was included as 15th seed thanks to her protected ranking.
Providing she is fit to play, she will take on American Julia Boserup.
Defending champion Garbine Muguruza was handed a tricky first round as she will take on the 2010 champion, Italian Francesca Schiavone.
On her possible path to the final, the fourth-seeded Spaniard could also face American Venus Williams.
World number one Angelique Kerber will open her campaign against Ekaterina Makarova.
Several top names will not feature in this year's tournament as 18-time grand slam champion Roger Federer is skipping the claycourt season, two-time champion Maria Sharapova was denied a wild card after returning from a doping ban, and three-time winner Serena Williams is expecting a child.
(Reporting by Julien Pretot; Editing by Hugh Lawson)
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