Two-time Queen's champion Matteo Berrettini lost in straights sets on his return from injury as his grass season started poorly in Stuttgart.
The 2021 Wimbledon finalist was beaten 6-1 6-2 by fellow Italian Lorenzo Sonego for only a second loss on grass in 22 matches.
Meanwhile, at 's-Hertogenbosch in the Netherlands, Canadian Milos Raonic claimed his first Tour-level win after nearly two years out with injuries.
He beat Serb Miomir Kecmanovic 6-3 6-4.
Raonic, Wimbledon runner-up in 2016, said he was still taking his recovery "day by day" after a "heartbreaking" period in which a series of injuries disrupted his career.
"It's been a real pleasure to get to play in front of people. I didn't get to hit a single tennis ball for a full year," former world number three Raonic, 32, said after his victory over fifth seed Kecmanovic.
"It was pretty nerve-wracking, I forgot that feeling. To be honest with you, it might have been a little bit easier if I played in front of nobody today.
"It's been a little heartbreaking a lot of the time when I couldn't do anything and it's nice for me to be here one more time.
"I get the chance to be on court, I get the chance to play, I get the chance to compete, to put in the work, and I get a chance to see how far it takes me, so I'm thankful."
At the Stuttgart Open, the 27-year-old Berrettini was competing for the first time since being forced to withdraw from the Monte Carlo Masters in April because of an abdominal injury.
He missed Wimbledon last year after he tested positive for coronavirus but the Italian, ranked 21 in the world, had enjoyed a series of excellent run of results on grass in the past couple of seasons before being dismantled by Sonego on Monday.
Fellow Italian Lorenzo Musetti, 21, the world number 17, began with a 7-6 (7-4) 6-3 win over Croatia's Borna Gojo following his run to the French Open fourth round.
France's Richard Gasquet, 36, beat American Christopher Eubanks 7-6 (7-2) 6-4 to set up a second-round meeting with Greek top seed Stefanos Tsitsipas, who received a first-round bye.