Murray failed to reach the next round after being beaten 6-1, 1-6, 6-4 by Pouille, who took the opening set in just over 30 minutes, The Independent reported.
Murray showed some fight in the second set, breaking Pouille in the first game and going on to level the match in convincing style.
But he could not edge ahead and Pouille held his serve in the 10th game of the final set and claim a deserved victory.
The former British No. 1 is refusing to panic though as he continues his comeback from 11 months out injured, and believes there are plenty of positives to pick out of the performance in Cincinnati.
“I only lost four more points in the match than him,” Murray said. “It was tight. He’s a top 20 player. If I can improve by 10, 15 percent, you turn a lot of those matches around.
“So I think also as the year goes on, maybe some of the events I play are maybe not as strong maybe later in the year, so draws can be a little bit different.
“But, yeah, you need to try and string more matches together. But it’s tricky in these events. If you’re not seeded, you play top, top quality players early on.”
The defeat leaves Murray facing a difficult decision over whether he should compete in the year’s final Grand Slam at Flushing Meadows in two weeks’ time. The former world No. 1 has still only played seven competitive matches since returning from his hip injury, and despite coming through three consecutive three-set matches in Washington, he was then forced to withdraw from the quarterfinals to prevent any risk of injury or fatigue.
“I kind of need to see once I’m in that position,” he added, ahead of the start of the US Open on Monday August 27. “I have played, four three-set matches and a couple long ones in Washington. Although I didn’t feel great, I managed to get through them.
“Hopefully with another couple of weeks and training, and I’m still quite early in this process, I think that’s the seventh match I have played, so hopefully each week will feel better and I can keep working on things.”