RIO DE JANEIRO: Novak Djokovic shook his head and placed his palm over welling eyes on his way to the locker room after a first-round Olympic exit, devastated he might never realize his goal of adding a gold in singles to a substantial collection of Grand Slam titles.

"I mean, no doubt, it's one of the toughest losses in my life, in my career," Djokovic said later, shaking his head and speaking in subdued tones. "Not easy to handle."

The Serb was hardly alone in his disappointment on Day 2 of the Rio de Janeiro Games: He was one of three No. 1 seeds to exit the tennis competition in a wild span of 12 hours.

Djokovic's 7-6 (4), 7-6 (2) setback Sunday night was caused in large part by ferocious forehand after ferocious forehand from a resurgent Juan Martin del Potro of Argentina. That surprising result followed losses by the top-seeded duos of Serena and Venus Williams of the United States — who entered their match with a 15-0 Olympic record and three gold medals as a pair — in women's doubles, and Nicolas Mahut and Pierre-Hugues Herbert of France in men's doubles.

The second-seeded men's doubles duo of Andy and Jamie Murray departed, too.

"Got to take it on the chin," said Jamie, the older brother of two-time Wimbledon winner Andy, "and move on."

Sunday began with 25 mph winds that delayed the start of play on eight of Rio's nine tennis courts for about 2 hours, and then came so many startling outcomes.

None was more significant than 2009 U.S. Open titlist del Potro's victory over 12-time major champion and No. 1-ranked Djokovic in a thriller before a raucous crowd. The match concluded with both men, who are friends, wiping away tears after a lengthy, warm embrace at the net, during which Djokovic offered what del Potro described as "really kind words."

Del Potro has dealt with three operations to his left wrist that kept him off the Grand Slam circuit for 2½ years, until Wimbledon last month, and even he acknowledged: "I didn't expect to beat Novak tonight."

Djokovic had won seven of their eight most recent meetings, and 11 of 14 overall, before Sunday. But this is the second time that del Potro came out ahead at an Olympics: He beat Djokovic to take the bronze medal in London four years ago.

Representing Serbia means a lot to Djokovic, who led his country to a Davis Cup title and carried its flag at the opening ceremony of the 2012 Games. He did earn a bronze at the 2008 Beijing Olympics, but to a guy with so much success, anything other than being the champion is not acceptable.

There is still a shot at gold in doubles in Rio — he and Nenad Zimonjic are into the second round — but as for singles, Djokovic will be 33 by the time Tokyo hosts the 2020 Olympics.

"The wounds are still fresh," Djokovic said. "But you've got to deal with it. It's not the first (or) the last time that I'm losing a tennis match. But Olympic Games, yeah, it's completely different."

This comes a little more than a month after a third-round loss at Wimbledon against Sam Querrey of the United States, and could add to the sense that Djokovic is not as unbeatable as everyone was beginning to think he was when he won the French Open in June to become the first man in nearly a half-century to win four consecutive major trophies.

With Djokovic out of the draw, 2012 gold medalist Andy Murray, who is seeded No. 2, becomes the favorite as he bids to become the first player to win consecutive Olympic singles titles. He won his opener in that event Sunday, 6-3, 6-2 against Serbia's Viktor Troicki.

Also chasing a repeat in singles: Serena Williams, who was the only No. 1 seed with a victory Sunday, albeit a patchy one, 6-4, 6-2 against Australia's Daria Gavrilova in singles.

Then Serena went back out on court to partner Venus, who has been ill and lost in singles on Saturday. They were beaten 6-3, 6-4 by the Czech Republic's Lucie Safarova and Barbora Strycova.

"We played terrible," Serena said, "and it showed in the results."

A common theme on this day.

After he and Jamie wasted five set points in the second tiebreaker of their 7-6 (6), 7-6 (14) loss against Brazil's Thomaz Bellucci and Andre Sa, Andy said he would skip mixed doubles and let his brother play with Jo Konta.

"I'll concentrate on the singles now," Andy said. "I'll get a day off tomorrow and recover. It's been a long day."