Wawrinka started off confidently against the Kazakh, winning the first set with ease. He staved off three set points in the second to hold for 5-5 but appeared tired. In the decisive third, Bublik pulled ahead early and wrapped up the match in just over two hours.
Wawrinka, 37, last competed on tour in March 2021 when he lost his opening match at the Qatar Open. He's had two surgeries on his left foot since then and months of difficult recovery.
"I'm still far away from where I want to be, but I think I'm in the right direction," Wawrinka said. Despite "a tough loss" to No. 35-ranked Bublik, the Swiss said it felt good to be on the court, packed with spectators, and playing competitively.
"It was much better than what I was expecting," Wawrinka said.
Still, the physical and mental fatigue made him consider he might have returned to the tour too soon. He has not lined up other tournaments but intends to spend more time on practice.
"I need a lot more ... and I need to work hard on my tennis and my physical condition," Wawrinka said.
Tsonga, 36, announced last week he will retire after the French Open, hoping to put the final touches on an injury-plagued career in front of his home crowd. A crowd of Tsonga's loyal fans cheered him on in the principality but he was no match for the No. 22-ranked Cilic, who breezed to victory.
Tsonga was disappointed he wasn't more competitive.
"I'm sad because it was my last Monte-Carlo. It's not always easy, but that's it,'' he said. "Maybe I have been on the tour for too long, but I do have some experience.''
The French Open starts on May 22 in Paris. Tsonga reached a career-high ranking of No. 5 in 2012, but has dropped to No. 220 following his latest lengthy injury layoff. That means he can't enter the main draw at Roland Garros automatically through his ranking, and will have to rely on being granted a wild card by organizers.