World number four Dominic Thiem suffered a fresh setback in his Roland Garros build-up when he was knocked out of the Lyon ATP event in his opening match on Thursday.
Top seed Thiem, 27, lost to Britain's 49th-ranked Cameron Norrie 6-3, 6-2 in just over an hour.
Thiem, a two-time runner-up at Roland Garros, won just one match at the Italian Open last week, arriving in Rome on the back of a semi-final run at Madrid where he belatedly started his clay court season.
"It was an unexpected victory," said Norrie. "I played well and I could not be happier."
Norrie will next face lucky loser Arthur Rinderknech after the 125th-ranked Frenchman shocked Italian sixth seed Jannik Sinner 6-7 (7/9), 6-2, 7-5.
Greek second seed Stefanos Tsitsipas, the champion at the Monte Carlo Masters, eased into the last eight against Tommy Paul of the United States 6-1, 6-4.
Tsitsipas has now reached the quarter-finals or better at nine of his 10 events in 2021.
French number one Gael Monfils, who on Tuesday won a match for the first time in 15 months, was knocked out by Japan's world number 60 Yoshihito Nishioka, 4-6, 6-3, 7-6 (7/2).
Nishioka had also defeated Monfils at the 2019 Davis Cup finals and his reward is a clash with Tsitsipas on Friday.