Novak Djokovic suffered a stunning defeat in his first ATP Tour match since February, the world number one losing in the second round of the Monte Carlo Masters to Alejandro Davidovich Fokina.

Djokovic's status as an unvaccinated player has limited his ability to compete on the tour this year. He missed the Australian Open in January after a saga surrounding his visa eventually resulted in his deportation on public health grounds, while laws around vaccination against COVID-19 in the United States prevented him from playing at Indian Wells and Miami.

Despite his inactivity, the Serbian - whose sole appearance on tour this year came during a run to the quarter-finals in Dubai - was expected to prevail on the clay against his Spanish opponent after receiving a bye in the first round.

But there were evident signs of rust in a mistake-riddled display against the world number 46, who remarkably emerged victorious to set up a meeting with either Dan Evans or David Goffin.

The tide looked to have turned in the second set tie-break, when an exquisite whipped forehand from Djokovic sent the match to a decider.

However, Djokovic, who committed 51 unforced errors, immediately surrendered the momentum by dropping serve in the first game of the third and he was broken twice more as Davidovich Fokina powered to a 6-3 6-7 (5-7) 6-1 victory in just under three hours.

"I knew that Nole hasn't had that confidence because he didn't play a lot," Davidovich Fokina said.

"This win is so special for me. I look at him every tournament. Here in Monte Carlo, full people [capacity], against the number one, I enjoy every moment."

Earlier, Evans saw off Benjamin Bonzi while Goffin, fresh off his triumph in Marrakech, came through against Jiri Lehecka to set up their second-round meeting.

Tenth seed Taylor Fritz defeated Monegasque wild card Lucas Catarina in three sets and 16th seed Lorenzo Sonego saw off Ilya Ivashka in straight sets. Laslo Djere, a semi-finalist in Marrakech, also progressed to the second round.