"Roger already told me some time ago that he had to renounce to play in our tournament because of a change in his clay season's schedule," tournament director Zljko Franulovic said Friday.
Top-ranked Nadal has confirmed his participation in the April 11-19 clay-court tournament.
Federer, a three-time finalist in Monte Carlo, could still ask for a last-minute wild card if he changes his mind, Franulovic said.
Nadal beat Federer 7-5, 7-5 in last year's final for his fourth straight Monte Carlo title.
"His only goal is to make history by achieving the unseen feat of winning five times in a row," Franulovic said.
Eight of the top 10 players are entered. Other than Federer, No. 7 Andy Roddick is the only player missing.