British number one Kyle Edmund lost 6-4 6-3 to Italy's Fabio Fognini in the first round at the Madrid Open.
Fognini, world number 12, took one hour and 30 minutes to secure victory as he broke Edmund's serve on four occasions.
Edmund could not recover after losing serve at 4-4 in the first set, or once he went 3-2 down in the second.
It is the Briton's fourth straight defeat, having lost to American world number 82 Denis Kudla in the first round of the Munich Open last week.
The 24-year-old has also lost to Diego Schwartzman in Monte Carlo and, after a first round victory over Ugo Humbert, to Jo-Wilfried Tsonga in Marrakech on clay this season.
Italian Fognini, who triumphed in Monte Carlo, will face either Australian John Millman or American Steve Johnson in round two.
World number two Rafael Nadal is preparing to begin his tournament with a second-round match against Canada's Felix Auger Aliassime.
A five-time champion in Madrid - most recently in 2017 - Nadal has been struggling with a virus as he aims to improve on back-to-back semi-final defeats.
The Spaniard lost to to Dominic Thiem in Barcelona and Fabio Fognini in Monte Carlo as he failed to defend either of his titles in April.
"I've been going through a virus. The positive side is I've been able to train at least an hour-and-a-half [per session]," said 32-year-old Nadal.
He added: "I hope that tomorrow is going to be a bit better. It's true that when you have this virus and stomach viruses, the body's a bit weaker. I'm a bit better than yesterday and yesterday was better than the day before.
"There is a bit more risk of injuries. But of course, this is a very important tournament for me and I hope to be ready. Barcelona was a positive improvement for me. I'm building up my game with more confidence than I had in Monte Carlo. I'm enjoying training and I enjoy playing each day."