JOIN USFour-time gold medallist Venus Williams, suffering with a virus, slumped to her first ever opening round loss at an Olympic Games, joining jet-lagged Agnieszka Radwanska at the exit door.
American fifth seed Williams, the singles champion in 2000 and, at 36, the oldest woman in the draw, lost to Belgium's Kirsten Flipkens 4-6, 6-3, 7-6 (7/5) in a three-hour centre court marathon.
Williams, who has also captured three doubles golds with sister Serena, had her opportunities, leading 3-1 in the second set and 4-1 in the decider.
But despite the encouragement of watching US Secretary of State John Kerry, she ran out of steam at the crucial moments, noisily coughing throughout the closing exchanges.
"She had been ill for a few days with a bad virus. She had an upset stomach and she was coughing up a lot, you could see she was really struggling," said US captain Mary Jo Fernandez, who faced the media in Williams' place.
Williams now faces a battle to be fit for Sunday's opening doubles with Serena.
"Fingers crossed, she'll be OK. I would be highly surprised if she didn't play. It's been her goal to play in her fifth Olympics and she wants to win a medal so badly."
Flipkens was just two points away from defeat in the ninth game of the decider and rated her win as "in the top two" of her career after her victory over Petra Kvitova at Wimbledon in 2013.
"To beat Venus, one of the biggest champions, gives me goosebumps," said the 30-year-old, playing in her first Olympics.
Fourth seeded Radwanska was also a high-profile casualty, slumping to a 6-4, 7-5 loss against China's world number 63 Zheng Saisai.
The Pole only arrived in Rio on Wednesday night after having to fly from Montreal, where she competed last week, to New York to Lisbon and then to Rio.
In all, she was on the move for 55 hours and covered around 14,000 kilometres.