Spanish No.6 David Ferrer looked comfortable as he beat France's Benoit Paire 6-3 6-3 6-2.
Nishikori, meanwhile, became the first Japanese man in 75 years to reach the French Open's fourth round, beating Frenchman Benoit Paire.
"It was not very comfortable and it affected my game, " Nadal told reporters ahead of his third-round tie with Frenchman Benoit Paire.
Frenchman Benoit Paire beat Marcel Granollers 6-1, 6-0 to advance to his first Masters semifinal and will face Roger Federer in the last four.
He will start his 53rd grand slam tournament against 46th-ranked Frenchman Benoit Paire, and as second seed he cannot meet two-time defending champion Djokovic until the final.
The 23-year-old became the first Japanese male to reach the last 16 at Roland Garros since 1938 as he beat home player Benoit Paire 6-3 6-7 (3-7) 6-4 6-1.
He next plays No. 13-seeded Kei Nishikori, who became the first Japanese man in 75 years to reach the fourth round at Roland Garros, beating Benoit Paire 6-3, 6-7 (3), 6-4, 6-1.
Richard Gasquet became the first player to win twice on the ATP Tour this year as he beat compatriot Benoit Paire 6-2 6-3 in Sunday's final of the Open Sud de France in Montpellier.
There is also the 24-year-old Frenchman Benoit Paire, whose flashy game and theatrical court presence have recently produced results, including a straight-sets victory over Juan Martin del Potro in Rome (Paire eventually lost to Federer in the semifinals).
Federer, who has been in fine form in Rome, was given a stern test by Paire, particularly in the first set, but used his experience to good effect to set up a repeat of his 2006 final in the Italian capital against Nadal.
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