Paris - Karen Khachanov's Paris Masters title defence ended at the first hurdle on Tuesday as the Russian lost 7-6 (7/5), 3-6, 7-5 to German Jan-Lennard Struff.
Khachanov beat four top-10 players, including Novak Djokovic in the final, to win the 2018 tournament, but was knocked out after an indifferent second-round display this time around.
The early exit ends the world number eight's slim hopes of qualifying for next month's ATP Tour Finals in London.
Struff, ranked 36th, will next face either former Bercy winner Jo-Wilfried Tsonga or Italian tenth seed Matteo Berrettini in the last 16.
The defeat brings a close to an up-and-down season on the ATP Tour for Khachanov.
The 23-year-old has broken into the world's top 10 for the first time, although he is now likely to drop out next week, and also reached his maiden Grand Slam quarter-final in June at the French Open.
But he has failed to reach an ATP final in 2019, despite making the last eight at tournaments seven times.
Canadian rising star Denis Shapovalov booked his spot in the second round for the first time when his opponent Gilles Simon retired injured with the opening set level at 2-2 in their match.
The 20-year-old Shapovalov, who won his maiden ATP title in Stockholm a fortnight ago, will play Monte Carlo Masters champion Fabio Fognini in round two.
Lucky loser Corentin Moutet became the fifth Frenchman to reach the last 32 this week with a 6-4, 1-6, 6-3 win over Serbia's Dusan Lajovic to set up a tie with world number one Novak Djokovic on Wednesday.
"I don't want to say that I'm impressed by him or any other player," Moutet said of Djokovic.
"But I have a lot of respect for his career because he's been number one for many years ... I will try not to be unworthy and to be better than him."
Elsewhere, Kyle Edmund ended an eight-match losing streak by beating Ricardas Berankis 6-4, 6-3 to boost his hopes of being selected for Britain's Davis Cup finals squad.
Australian youngster Alex de Minaur, who lost to Roger Federer in the Basel final on Sunday, saw off Laslo Djere 6-1, 6-4, while Taylor Fritz won an all-American clash with Frances Tiafoe 7-6 (8/6), 3-6, 6-4.
Results from the second day of the ATP Paris Masters on Tuesday (x denotes seeding):
Jan-Lennard Struff (GER) bt Karen Khachanov (RUS x8) 7-6 (7/5), 3-6, 7-5
Corentin Moutet (FRA) bt Dusan Lajovic (SRB) 6-4, 1-6, 6-3
Kyle Edmund (GBR) bt Ricardas Berankis (LTU) 6-4, 6-3
Alex de Minaur (AUS) bt Laslo Djere (SRB) 6-1, 6-4
Taylor Fritz (USA) bt Frances Tiafoe (USA) 7-6 (8/6), 3-6, 6-4
Denis Shapovalov (CAN) bt Gilles Simon (FRA) 2-2 -- retired