Nadal has fallen to No. 7 in the ATP rankings since coming back from injuries, dropping his seeding to sixth, the lowest it's ever been at the clay-court major.
That left him more vulnerable than usual in Friday's draw, and bad luck put him in the same quarter as both Djokovic and 10th-seeded Grigor Dimitrov, and in the same half as Andy Murray.
Nadal has faced tough draws before. In 2011, 2013 and again last year, he beat three top 10 players to lift the Musketeers Cup. His record on the red clay of Roland Garros is 66-1, with his only loss coming in the fourth round in 2009.
"Everybody had their eyes on this potential clash between Nadal and Djokovic," tournament director Gilbert Ysern said. "It will be tough for the loser, because they seem to be the best players on clay at the moment."
But this season, Nadal arrived in Paris with his reign looking shaky. He has lost five times on clay this season, his worst run-up ever to tennis' second major.
Ysern said there was never any thought of bumping up Nadal's seeding to better protect him in the draw.
"Three or four years ago we thought about giving him a higher seeding when he dropped in the rankings because of a long lay-off due to an injury. But this year it's different, because his ranking dropped mainly due to his results on court," Ysern said. "We did not even think about it and he did not ask for it, it's not his style to ask for anything."
The task of drawing the names of the seeded men was given to defending women's champion Maria Sharapova, who will begin her campaign against 49th-ranked Kaia Kanepi. Nadal rubbed his chin and looked less than comfortable as Sharapova set to work.
With Djokovic, Nadal, the third-seeded Murray and 2013 runner-up David Ferrer all in the same half of the draw, the road for Roger Federer on the other side opened up.
To reach what would be his sixth final in Paris, and first since losing to Nadal in 2011, the 17-time Grand Slam champion could have to overcome 2014 Australian Open champion Stan Wawrinka in the quarterfinals.
Wawrinka, seeded eighth, is one of three top 10 players in Federer's half of the draw. Fifth-seeded Kei Nishikori and fourth-seeded Tomas Berdych are the other two. They could meet in the quarterfinals, with a potential semifinal against Federer or Wawrinka to follow.
In the women's draw, 19-time Grand Slam champion Serena Williams faces a potential third-round match against former No. 1 Victoria Azarenka, seeded 27th.
Williams will face a qualifier in the first round. Her sister Venus, however, was drawn to open against Sloane Stephens, a semifinalist at the 2013 Australian Open who has reached the fourth round for the last three years at Roland Garros.