Nadal was set to face Fernando Verdasco this afternoon in the second round.
But the Spaniard will not take to the court having withdrawn from the tournament due to an abdominal injury.
It follows on from Roger Federer receiving another bye into the third round after Milos Raonic pulled out of the Paris Masters.
Nadal’s withdrawal will also mean he will lose his world No 1 ranking to Novak Djokovic on Monday.
The 32-year-old has been out of action since retiring from his match against Juan Martin del Potro at the US Open two months ago.
He didn’t participate in the Asian tour as he wanted to recover from the knee injury he picked up at Flushing Meadows.
But Nadal has suffered another setback this week, citing a different injury entirely.
It also places doubt over whether or not he will be fit enough to play at the ATP Tour Finals in London.
The season-ending tournament takes place from November 11 to November 18 with the top-ranked players taking part.
He withdrew from the 2017 ATP Finals due to an ongoing knee injury, being replaced by fellow Spaniard Pablo Carren Busta.
Speaking earlier this week, Nadal admitted finished the season as world No 1 wasn’t a personal goal of his.
“No, I get injured and I get injured in an important part of the season twice,” he said.
“At the beginning of the season, missing two Masters 1000s, a 500, the Australian Open and then I get injured at the US Open and I miss again Beijing, Shanghai. So too many tournaments lost.
“My main goal is to be back on court, keep being happy playing tennis and then things that can happen or not, let’s see.
“I’m going to fight as strong as I can to win as many matches as possible and of course I would love to be No 1 but I am just here to try my best every day.”