The Italian looked off from the outset of his match against rival Carlos Alcaraz on Monday and, after quickly falling behind 5-0 in the first set, retired from the match, saying he "didn't feel great" and apologising to the disappointed fans in Ohio.
Tennis World USA reported that Sinner was battling a high fever and flu symptoms the night before and during his match with Alcaraz.
Sinner also mentioned the punishing heat and humidity during his match against Alcaraz, calling it "one of the hottest tournaments we played". He then announced that he had withdrawn prior to his US Open mixed doubles match on Tuesday.
Sinner and world No 2 Alcaraz have separated themselves from the pack, having won the last seven major titles between them.
While Sinner has compiled a stellar 31-4 win-loss record this year, three of those defeats have come at the hands of the 22-year-old Spaniard, who rolls into Flushing Meadows with a tonne of momentum and a chance to grab the world No 1 ranking from Sinner.
Prior to Monday's final, Sinner looked unstoppable, not dropping a set in his first tournament since winning Wimbledon for his fourth Grand Slam title in July.
"I feel like it was a very positive week," Sinner, who won the Cincinnati title last year, said on Monday.
"Making finals of a Masters event, it's always an amazing achievement. So we'll keep going, keep pushing. I have some points where I need to improve if I want to go far in the US Open. And it was a good test this week, trying to understand where my level is."
He said his focus was firmly on the biggest stages the sport has to offer.
"I love Grand Slams a lot. These are the main tournaments for my season and for my career. So US Open is going to be a tough tournament, but at the same time, I'm looking forward to it. If I'm ready, physically and mentally, I will be ready to push.
"So now I have a couple of days of recovery, and then we get back to work, and hopefully we'll be ready.
Alcaraz confident
Health permitting, all signs point to the duo meeting again in a major final and completing a season-defining trilogy after Alcaraz beat Sinner in an epic five-setter to retain his French Open trophy in June before surrendering his Wimbledon crown to the top-ranked Italian last month.
Although Alcaraz has excelled on grass and clay, hardcourt consistency has eluded him on the grandest stage following his 2022 US Open triumph, but the five-times major champion is approaching the New York showpiece starting on Sunday with renewed belief.
"I'm feeling a lot of confidence, playing on a different surface," said Alcaraz, whose US Open triumph three years ago ensured that he became the youngest world No 1 since the inception of the ATP rankings in 1973.
"New York is a place that I love playing in. It's where I got my first Grand Slam and I appreciate the love and support that I receive there every year that I go."
The Cincinnati champion has gone on to capture the US Open trophy in the previous two years, with Serbian Novak Djokovic prevailing in 2023 before Sinner's success last time, and a philosophical Alcaraz is hoping to keep that run going.
"I'm accepting everything that's happening to me and trying to learn to be a better person and player from the experiences that I'm living in the last three to four months," he said on the Tennis Channel.
"I'm doing great things that I'm really proud of, so I'm going to try and do the same things in New York."
