The 14-time Grand Slam champion, just three behind all-time leader Roger Federer, bombed out in the opening round of the Australian Open to fellow Spaniard Fernando Verdasco.
In only his second first-round loss at a major tournament, Nadal, 29, fought for four hours, 41 minutes before the inspired Verdasco won 7-6 (8/6), 4-6, 3-6, 7-6 (7/4), 6-2.
But Nadal was not seeking excuses as he heads home to work towards his favourite Grand Slam at Roland Garros, where he is a nine-time champion, in late May.
“The match is a tough loss for me, especially because it’s not like last year when I arrived here playing bad and feeling myself not ready for it,” Nadal said.
“This year was a completely different story. I have been playing and practising great and working so much.
“You know it’s tough when you work so much and arrive at a very important event and you’re going out too early.
“It’s tough, but at the same time, I know I did everything that I can to be ready for it. Was not my day. Let’s keep going. That’s the only thing.
“There is no more thing to do than keep practising hard, keep practising the same way that I was doing the last four, five months.”
Elsewhere, retiring Australian veteran Lleyton Hewitt beat compatriot James Duckworth in his opening round match of his farewell Open.
The two-time major winner and former world No.1 overcame Duckworth 7-6 (7/5), 6-2, 6-4 and will next face Spanish eighth seed David Ferrer.
Former champion Stan Wawrinka also advanced to the second round after his Russian opponent Dmitry Tursunov retired with an injury.
The Swiss fourth seed was leading 7-6 (7/2), 6-3 when Tursunov called it quits at the start of the third set.
Britain’s Andy Murray is safely through to the second round along with Spain’s David Ferrer, Canada’s Milos Raonic and Frenchman Gael Monfils.
Australian Bernard Tomic overcame Uzbekistan’s Denis Istomin in four sets but the match had to be stopped for around 15 minutes when a spectator suddenly fell ill.