The Spaniard, who had his right knee strapped during his third-round win on Thursday, said he wanted to try and be ready to face Filip Krajinovic in the last eight but that “it wasn’t possible to play”.
He did not say if he would be fit to play at the World Tour Finals in London later this month.
“Yesterday (Thursday), the pain was very strong but it was not the moment to stop,” Nadal told a press conference.
“I had treatment last night to try and be able to play today… But unfortunately it was impossible for me to return to the court in the same condition as last night. It is a sad day for me.”
The 31-year-old became the oldest man to secure top spot in the end of season rankings when he beat Hyeon Chung in his opening match on Wednesday.
Nadal has fought back this year from a series of injuries, winning the French and US Open titles.
He missed the end of the 2012 season and the start of the following year with a left knee injury, and struggled with a wrist problem as he failed to reach a Grand Slam semi-final in 2015 and 2016.
But he allayed fears this fresh setback would lead to another lengthy spell on the sidelines.
“I had a long year, a lot of matches. I pushed the body,” Nadal added.
“We are at the end of the season. It’s normal that these kind of things happen. The knee is always, you know, bothering a little bit, but sometimes it’s worse, and now is a little bit worse.”
He called the trainer to have his knee taped after the second set of his last-16 win over Pablo Cuevas, before insisting he would be fit to play at the season-ending event in London.
But the 16-time Grand Slam champion then ended his bid for a first Bercy title and a record 31st Masters crown, a serious blow for a tournament which is already missing the likes of Roger Federer, Andy Murray and Stan Wawrinka.
If Nadal pulls out of the Tour Finals, it would leave Federer as the only member of the ‘Big Four’ in the year-ending event for the first time since 2005.
“I’m going to do my treatment, do my best to be playing in London, but I cannot talk about that now because (it) is a day that is tough enough for me to pull out from here,” he said.
“For me it’s not about London. For me it’s about longer term.
“And longer term I’m going to do the treatment I believe that (is) going to be more safe and more important to keep playing tennis as long as possible.”
World number 77 Krajinovic, who had never been past the second round of a Masters tournament before, now progresses to his first ATP semi-final of the season against either Juan Martin del Potro or John Isner on Saturday.
“I did not expect this at all, I was ready to play but then I heard he had pulled out,” said the Serb.
“I’m going to enjoy today and then see how it goes tomorrow (Saturday).”
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