Kyle Edmund was forced to retire from his second-round match at the French Open against Pablo Cuevas, leaving Johanna Konta as the last Briton in the singles draw.
The British No 1 has endured a torrid few months with injury and illness and his first-round epic lasting two days against Frenchman Jeremy Chardy appeared to take its toll on Thursday.
It was a curiously passive performance from Edmund as he lost the opening two sets and, after going 7-6 (7-3) 6-3 2-1 down, he called the doctor.
It was not immediately obvious what was wrong but, after a lengthy chat, Edmund shook his head and then the hand of Cuevas.
Edmund had been looking to reach round three for the third year in a row, but he was up against Cuevas, ranked 47.
Cuevas is a classic clay-court specialist, he has had a lot of match wins on the surface this season, including reaching the final of the ATP Tour event in Estoril last month.
Edmund ended a five-match losing run over Jeremy Chardy in the previous round
The 24-year-old began poorly, dropping serve in the second game, but retrieved the break to level at 4-4 and withstood pressure from Cuevas to force a tie-break.
He had played a fine tie-break in his opening match against Chardy but this one was a different story, and things did not improve in the second set, where he lost the last four games.
Cuevas will take on last year's French Open finalist Dominic Thiem next
It was not obvious that Edmund, who struggled with a knee injury for the first two months of the season, was having physical difficulties but it was clear he was frustrated, the Briton slamming a ball down and shouting at himself after being broken in the seventh game of the second set.
Whatever the problem, it was clearly serious enough for Edmund to feel he could not continue, and Cuevas recorded the win to set up a meeting with Dominic Thiem.
The Austrian fourth seed defeated Kazakhstan's Alexander Bublik 6-3 6-7 (6-8) 6-3 7-5.
Dominic Thiem has been made to work very hard through his first two rounds
Thiem is seen as one of the only men who could challenge Rafael Nadal and Novak Djokovic, but he has been made to work very hard through his first two rounds.
After being taken to four sets by Tommy Paul in round one, the Austrian trailed Bublik by a break in the fourth set but finished strongly.
Novak Djokovic had no problems brushing aside Swiss lucky loser Henri Laaksonen 6-1 6-4 6-3.
It appeared the match might not even be that close when Djokovic allowed his opponent just five points in the first five games but Laaksonen did at least dig in to make it somewhat competitive.