MONACO — Top-ranked Novak Djokovic suffered his earliest loss in three years when he was stunned by 55th-ranked Jiri Vesely 6-4, 2-6, 6-4 in the second round of the Monte Carlo Masters on Wednesday.

It was also his 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.

Defending champion 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.

“I was playing really, really bad,” Djokovic said. “I wasn’t feeling any freshness.”

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.

“There is the proof that nobody is unbeatable,” Djokovic said. “It’s not easy to lose the match in terms of accepting it, but I have to congratulate my opponent.”

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.

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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.

His previous second-defeat was at the 2013 Madrid Masters.

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.

Djokovic, at least, is looking forward to a rest.

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

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“I have to move on, it’s already behind me. I’ve had an incredible start to the season, and this match will not disturb my preparation for the rest of the season.”

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.

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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 percent 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 won 7-5, 2-6, 7-6 (5) against Uruguayan Pablo Cuevas, and No. 16 Benoit Paire of France downed Joao Sousa 6-4, 6-3.

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Paire next faces No. 2 Andy Murray, while Raonic takes on Dzumhur.