The Spaniard was beaten 7-6 (7), 6-2 by eighth-seeded Stan Wawrinka in the Italian Open quarterfinals Friday; his fifth loss on clay this season.
Nadal wasted four set points in the tiebreaker, surrendering a 6-2 lead.
"I didn't have enough leg in some moments today. He played crazy. He hit amazing shots in a lot of moments, and especially important ones," Nadal said. "At 6-2 he played a lot of good points.
"I am not very happy with the way I played," Nadal added. "During the night the ball is bigger, the bounces are not that high. So he has the chance to go for it. And he was on fire."
The last time Nadal was beaten so many times on his favourite surface was 12 years ago — in his rookie season.
Nadal has won the French Open nine of the past 10 years. But he's struggling to get back to his best after a wrist injury and an appendectomy last season.
On Monday, Nadal dropped out of the top five in the ATP rankings for the first time in 10 years — falling to No. 7. That will give him a tough draw in Paris, where play starts next weekend.
"I am ready to accept the challenge," Nadal said. "If I go to Roland Garros (and) I lose (and) I don't play well, life continues. It's not the end of the world. I won so many times there. I don't want to (win) 15 Roland Garros. That's for sure. It's normal that I can lose. Losing is part of life."
But, he added: "I am sure that I can be competitive."
Nadal had won all 12 of his meetings with Wawrinka until the Swiss player beat him in last year's Australian Open final for his first Grand Slam title. Now, Wawrinka has won two straight against the Spaniard.
"I was looking for some win to get my confidence back and this is a perfect match for that," Wawrinka said. "To beat Rafa on clay is something amazing for me."
Wawrinka raised his arms in triumph to celebrate and sent a message to his semifinal opponent — fellow Swiss player Roger Federer. Handed a pen to sign a camera lens, Wawrinka scribbled, "See you tomorrow R.F."
Federer kept up his pursuit of an elusive title with a 6-3, 6-3 win over sixth-seeded Tomas Berdych.
Rome and Monte Carlo are the only Masters series titles that the 17-time Grand Slam champion has never won.
Top-ranked Novak Djokovic, meanwhile, was pushed to three sets for the third consecutive match in a 6-3, 3-6, 6-1 win over fifth-seeded Kei Nishikori.
Djokovic's semifinal opponent will be seventh-seeded David Ferrer, who beat David Goffin of Belgium 6-2, 4-6, 6-3.
In the women's tournament, two-time Rome champion Maria Sharapova defeated former No. 1 Victoria Azarenka 6-3, 6-2.
Sharapova will face Daria Gavrilova of Russia, who beat Christina McHale of the United States 6-2, 6-4 in a match of two qualifiers.
Second-seeded Simona Halep routed qualifier Alexandra Dulgheru 6-1, 6-0 in an all-Romanian match. Halep will next face 10th-seeded Carla Suarez Navarro of Spain, who eliminated last week's Madrid Open champion Petra Kvitova 6-3, 6-2.
Djokovic, the defending champion also went three sets against Nicolas Almagro and Thomaz Bellucci in his opening two matches. Still, he extended his winning streak to 20 matches.
"(There were) ups and downs for my side in all three matches," Djokovic said. "This is what it takes to win, just finding the proper way and managing to perform your best when it matters."
Federer fell behind a break midway through the first set but recovered immediately and cruised from there.
"From the baseline I was playing very well." Federer said. "My serve was not quite there from the beginning. I was hitting too many second serves and he was able to take advantage of that and break early. So it was important to pick it up on the serve, which is maybe the easiest thing to do."
"I felt good again on the return and (was) moving well, so as the match went on I got better and better," he added. "The wind picked up in the second set — that's when I think Tomas didn't play so well anymore and I was able to get the job done."
After winning a title on clay in Istanbul two weeks ago, Federer lost his opening match to Australian Nick Kyrgios at last week's Madrid Open. But he has played solidly here, also beating Kevin Anderson of South Africa in straight sets in his opening match.
Making his 15th appearance at the Foro Italico, Federer is a three-time finalist. He was beaten by Felix Mantilla in 2003, by Nadal in a fifth-set tiebreaker in 2006, and by Nadal again in 2013.
Andrew Dampf can be followed at www.twitter.com/asdampf