MONACO, Monaco - Top-ranked Novak Djokovic chose to be philosophical after losing in the second round for the first time in three years on Wednesday, calling it "proof that nobody is unbeatable" after surrendering his Monte Carlo Masters title in a shock 6-4, 2-6, 6-4 loss to 55th-ranked Jiri Vesely.

His previous second-round defeat was at the 2013 Madrid Masters to Bulgarian Grigor Dimitrov, a vastly talented shot-maker with a far higher reputation than Vesely, an aspiring Czech player with one career title compared to the 63 for 11-time Grand Slam winner Djokovic.

It was also Djokovic's first loss in a completed match since November, having retired from a match in February with eye infections. This was his first match of the year on clay.

"There is the proof that nobody is unbeatable," the Serb said. "I have to move on, it's already behind me."

Djokovic saved a match point when he was serving against Vesely in the ninth game. But the Czech, who had never beaten a top-10 player, sealed the win on his second match point in the next game when Djokovic's forehand landed wide.

It was his first loss in a Masters-level event since August. Since then, he'd won nine of 10 events, including two grand slams, four consecutive Masters titles, and the ATP Finals.

"I was playing really, really bad," Djokovic said. "I wasn't feeling any freshness."

The 22-year-old Vesely, who named Roger Federer as his idol when growing up, was understandably staggered by his win.

"It's something amazing. When I went on court, I had completely different thinking," Vesely said. "I hoped to win a game, hoped to do well. I really didn't think I could beat Novak today."

He did soon notice, however, that Djokovic was off his game.

"Novak wasn't at his best level, that's for sure, and he made a lot of mistakes from the beginning," Vesely said. "That's what gave me a little bit more confidence, creating the rallies. I didn't give him too much rhythm."

Earlier, eight-time Monte Carlo champion Rafael Nadal dropped serve twice and still beat Aljaz Bedene of Britain 6-3, 6-3 in the second round, but last year's runner-up, No. 6 Tomas Berdych, lost to 99th-ranked Damir Dzumhur of Bosnia 6-4, 6-7 (1), 6-3.

In another upset, No. 9 Richard Gasquet lost to wild card Lucas Pouille 4-6, 7-5, 6-1 in an all-French match. But it was nothing compared to Djokovic's loss.

Since January 2015, Djokovic had reached 19 finals in 21 tournaments, winning 15 — and the Serb was 28-1 on the year heading into Monte Carlo, having not dropped a set when winning the Miami Masters two weeks ago.

Athough Djokovic looked rusty, it was difficult to predict a second defeat of the season after his retirement to Spain's Feliciano Lopez in the Dubai quarterfinals.

"I will get a long break now," Djokovic said. "The time off will serve me well, mentally mostly."

In terms of ranking, this was Djokovic's worst since June 2010, when he lost to 74th-ranked Xavier Malisse on grass in the third round at Queens.

Vesely, whose lone ATP title came more than a year ago in Auckland, did not face a break point in the first set, and concluded it confidently on serve.

Djokovic lost his opening two service games in the third set, and an ace from Vesely put him 4-2 up.

Djokovic saved the first match point with an angled backhand volley at the net, but a loose forehand on the next gave Vesely his biggest ever win.

Nadal, meanwhile, was broken for a second time when serving for the match against Bedene at 5-2, but the Spaniard broke straight back to seal victory.

The fifth-seeded Nadal, who won the last of his titles here in 2012, next faces 12th-seeded Dominic Thiem of Austria.

"He has a great serve and a great forehand," Nadal said of Thiem. "I need more victories to be 100 per cent confident."

No. 4 Stan Wawrinka, the 2014 champion, also advanced past Philipp Kohlschreiber 7-6 (2), 7-5 into the third round and next faces No. 15 Gilles Simon of France.

In other second-round matches, No. 10 Milos Raonic of Canada, No. 11 David Goffin of Belgium, No. 13 Gael Monfils and No. 16 Benoit Paire of France all advanced to the third round.

Paire next faces No. 2 Andy Murray.