Jo-Wilfried Tsonga made his return after a seven-month absence at the Moselle Open, but the Frenchman was unable to get past defending champion Peter Gojowczyk in Metz.
Tsonga, an Australian Open finalist 10 years ago, had not played an ATP event since February due to a knee injury and he was back on home soil at a tournament he has previously won on three occasions.
He won the first set against Gojowczyk too but, the 29-year-old was able to stave off all three break points he faced across the match, also landing 17 aces en route to a victory in one hour and 45 minutes.
The German's title defence gets no easier, though, as he faces top-seed Kei Nishikori next in the Japanese's first tournament since he reached the US Open semi-final.
Nikoloz Basilashvili was the only seed in action on Tuesday and the man ranked fifth beat qualifier Kenny de Schepper in straight sets, while Frenchman Ugo Humbert was able to overcome Bernard Tomic in three sets.
In St Petersburg, the defending champion also progressed past the first round as sixth seed Damir Dzumhur beat Lucas Miedler 7-5 6-3.
Dzumhur was a double break down in the first set but would finally wake up to see off an opponent who had beaten Viktor Troicki in qualifying.
Daniil Medvedev encountered few issues in a 67-minute 6-4 6-1 victory over Joao Sousa, while Jan-Lennard Struff was able to avoid facing a break point in a win over Andrey Rublev that set the German up for a second-round tie with Dominic Thiem.
