Novak Djokovic has crashed out of the US Open on the opening night after he battled physically in humid conditions against World No.49 Mariano Navone. The 24-time grand slam champion lost the opening set against his Argentine opponent, before righting the ship to take the second and third.

However his body let him down from there and he could barely move in the fifth set, losing 6-7 (5-7) 7-5 6-4 2-6 1-6. The Serb endured cramps and was spotted vomitting on the side of the court at one point, while also shedding tears late in the match.

Novak Djokovic, Casper Ruud and Marin Cilic.

Novak Djokovic (L) crashed out while Casper Ruud and Marin Cilic (R) both withdrew from the US Open. Image: Getty

Early in the second set, the 24-time grand slam champ looked at his box and said: “I have nothing right now”. The 39-year-old took a medical timeout before the fifth set and received treatment on his back, but it did little to help as Navone capitalised for one of the biggest wins of his career.

It’s the first time Djokovic has lost in the opening round of a grand slam since the Australian Open in 2006 when he went down to Paul Goldstein.

It came after two-time grand slam champion Barbora Krejcikova became the first big casualty, while the tournament was also rocked by two big name withdrawals at the 11th hour. Casper Ruud and Marin Cilic both pulled out of the event before their first-round matches and had to be replaced in the draw.

Ruud was the 19th seed at the US Open, but will miss the event for the first time in his career. “Unfortunately, my back hasn’t healed as quickly as we had hoped,” said the 2022 runner-up at Flushing Meadows. “We’ve been optimistic that I would recover in time, but my team and I have decided that we need to think long term and give my body the time it needs.

“I’m very sad to announce that I have to withdraw from this year’s US Open singles event. It’s never easy to miss a grand slam, but I know this is the right decision. I’ll take the time I need to recover properly and come back stronger. Thank you for all the support.”

Arthur Gea takes Ruud’s spot in the draw and will take on Juan Manuel Cerundolo in the first round. Ruud wasn’t the only high-profile withdrawal on Sunday with 2014 US Open champion Cilic also pulling out.

Cilic was due to take on Andrey Rublev in the opening round, but is replaced but lucky loser Otto Virtanen. The 37-year-old Cilic didn’t specify why he had to withdraw, but joins other big names like Jannik Sinner, Jack Draper, Joao Fonseca and Holger Rune to pull out.

Barbora Krejcikova at the US Open.

Barbora Krejcikova became the first big casualty at the US Open. (Photo by Dustin Satloff/USTA via Getty Images)

Barbora Krejcikova becomes first big-name casualty

As for Krejcikova, the former French Open and Wimbledon champion crashed out at the first hurdle in a 6-7 (4) 2-6 loss to Uzbekistan’s 88th-ranked Kamilla Rakhimova. Cameron Norrie was another big-name casualty in the early going, losing to Luca Van Assche in four sets.

For the Aussie contingent, Talia Gibson, Storm Hunter and Adam Walton all lost before Taylah Preston scored a 6-3 6-3 win over American Alycia Parks. “It’s a hard one to swallow,” Gibson said after blowing the lead. “Most of the time it’s who makes the most unforced errors on the court who comes away with the loss and today that was me, so it’s just something to learn from.”