The Serb said he was too exhausted to put up a fight in the third set.
"I collapsed," Djokovic said. "I just ran out of gas completely ... If you can't stay in the rally, not feeling your legs on the clay, it's mission impossible."
Djokovic had beaten Davidovich Fokina in straight sets twice last year, in Rome and at the Tokyo Olympics.
Djokovic could not defend his Australian Open title in January after he was deported from the country for not being vaccinated. He had to skip tournaments in Indian Wells, California, and Miami because he couldn't travel to the United States for the same reason.
The authorities in France and Monaco lifted most COVID-19 restrictions last month, allowing people who aren't vaccinated into the country and back into restaurants, sports arenas and other venues.
That means Djokovic will be able to play at the French Open, which remains his "big goal of the clay season."
"I knew that it's going to take some time for me to really feel my best on the clay," Djokovic said. "I have to accept defeat and keep working ... and hopefully build my form for Roland Garros."
The French Open starts on May 22 in Paris.
- AP