Murray, back on court after pulling out of the Citi Open in Washington, had won all four previous meetings with the Frenchman but was below par and too inconsistent against the 16th seed.

Former world No 1 Murray, playing only his fourth tournament in 13 months as he continues his comeback from hip surgery, was broken in the first game as Pouille took the  opening set in just over 30  minutes.

Murray hit straight back to level the match after winning the second set 6-1 in convincing style.

Andy Murray serves in the second set against Lucas Pouille in Cincinnati last night. Picture: Getty.

He broke Pouille in the first game and never looked back, stepping on to the front foot, finding his range and playing more aggressively.

Pouille was broken for a second time to trail 4-1 and, after Murray comfortably held, the Frenchman lost his serve again in the seventh game to send the match into a decider.

But Murray lost his way again and could not contain the impressive shot-making of Pouille, who dominated the third set to win in an hour and 53 minutes.

Pouille pounced on Murray’s nervous start to the decider as the Briton double-faulted on the first point before being broken in the opening game. Pouille moved comfortably into a 2-0 lead and although Murray held serve in the next, he failed to convert a break point in the fourth game and fell 3-1 behind.

Murray pulled it back to 5-4, having saved match point on his serve as he trailed 5-3, but Pouille held his nerve to hold serve in the tenth game, taking the set 6-4 and sealing a deserved victory.

The defeat is not what Murray wanted as the countdown to the US Open continues. The final grand slam of the year, at Flushing Meadows in New York, starts on 27 August and Murray now doesn’t have another competitive match scheduled before then.

Earlier, world No 1 Rafael Nadal had pulled out of the Cincinnati tournament.

The 32-year-old Spaniard, who won the title in 2013, said he needed a rest following Sunday’s victory at the Rogers Cup in Toronto.

“I am very sorry to announce that I won’t be playing in Cincinnati this year,” Nadal wrote on Twitter.

“No other reason than personally taking care of my body and trying to keep as healthy as I feel now. I am very thankful to my friend, Andre Silva, tournament director of the Cincinnati tournament, who after speaking to him on the phone understood what I said and understands the situation.

“I am sure the tournament will be a success and I wish him and his team all the best. I am also sad for those amazing fans in Cincy who always gave me great support.”

Nadal, the 17-time grand slam winner, collected his 80th career title on Sunday by beating Greek youngster Stefanos Tsitsipas 6-2, 7-6 (7/4).

Andy Murray's US Open under cloud after defeat in Cincinnati