Daniil Medvedev was dumped out of the European Open in the first round following a shock 6-4 6-3 loss to Ugo Humbert.
World number five Medvedev was in action for the first time since his US Open semi-final defeat to eventual champion Dominic Thiem and the top seed in Hamburg was defeated in straight sets.
Humbert overcame Kevin Anderson and Fabio Fognini in straight sets at the Internazionali d'Italia last week and he claimed another impressive scalp – his first against a top-10 player – after an hour and 22 minutes.
The 22-year-old Frenchman ensured Medvedev did not enjoy his first match on clay since last year's French Open, and he will now face Jiri Vesely in the second round.
Reigning champion Nikoloz Basilashvili went down 6-4 6-3 to Roberto Bautista Agut, while third seed Gael Monfils bowed out with a 6-4 6-3 loss to Yannick Hanfmann.
Fognini came from a set down to beat Philipp Kohlschreiber, and Karen Khachanov rallied back from a double break down in the decider to progress at the expense of Jan-Lennard Struff.
Felix Auger-Aliassime downed Lorenzo Sonego 6-2 7-6 (7-2) and Cristian Garin got the better of Kei Nishikori in straight sets.