Second seed Stefanos Tsitsipas is out of the Paris Masters after a three-set defeat to in-form Frenchman Ugo Humbert, while another player has had to drop out with coronavirus.
Humbert, who won the European Open in Antwerp less than 10 days ago, edged a tight match where all three sets were decided by a tiebreak.
Despite squandering three match points is set two, Humbert went on to win 7-6 (7-4), 6-7 (6-8), 7-6 (7-3).
The Greek Tsitsipas received a bye into the round of 32, so has now lost two of the three matches he has played since losing in the semi-finals of the French Open.
Croatia's Marin Čilić, who at 32 is a decade older than Humbert and a previous US Open champion, awaits the French player in round three.
Čilić advanced to the third round via walkover after France's Corentin Moutet tested positive for COVID-19, forcing his withdrawal from the Association of Tennis Professionals (ATP) Masters 1000 tournament.
Belgian David Goffin was another seed to exit the competition today, losing to Slovakian qualifier Norbert Gombos 6-4, 7-6 (8-6).
US semi-finalist Pablo Carreño Busta swept aside Germany's Jan-Lennard Struff 7-6 (7-3), 6-2, keeping his bid to qualify for the end-of-season ATP Finals in London alive.
Some first-round matches were also played in the French capital, with Stan Wawrinka - a three-time Grand Slam winner and Olympic doubles champion at Beijing 2008 - among those in action.
Seeded 12th, Wawrinka bettered Dan Evans of Britain 6-3, 7-6 (7-3), while Canadian 10th seed Milos Raonic defeated Solvenia's Aljaž Bedene 6-3, 6-2.
Rafael Nadal - the top seed and a record 20-time Grand Slam winner - is among those in action tomorrow, up against fellow Spaniard Feliciano López.