Novak Djokovic struggled with the heat and humidity as he fell to a shock defeat by Argentina’s Thiago Tirante in the second round of the Cincinnati Open.

The 24-time Grand Slam champion dropped onto his hands and knees and took a medical timeout during the second set before eventually losing 2-6 6-4 6-4 to the South American, who is ranked 50th in the world.

Djokovic, 39, the world number five, was making his first appearance since losing to Jannik Sinner in the semi-finals at Wimbledon in July.

The Serbian had never failed to reach at least the last 32 of the tournament in Ohio since making his debut in it in 2005.

However, despite claiming the first set, Djokovic toiled badly after winning an 18-minute third game in the second set and appeared to vomit twice.

A physio and a doctor both provided on-court assistance and both players returned to the dressing rooms after the second set.

However, when play resumed Djokovic dropped serve in the ninth game of the third set and Tirante was able see out the match.

“This is the best win of my career,” said the Argentine.

“I managed the nerves of playing a legend like Novak. It was all so much pressure.”