The Spaniard withdrew from the final Grand Slam of the season on Wednesday because of his knee tendinitis problems.
Nadal was also forced to pull out of the London Olympics due to the same injury and subsequently withdrew from ATP Tour events in Toronto and Cincinnati.
Speaking at the Cincinnati Masters, Federer admitted that Nadal's absence from the US Open is a blow for the followers of the sport.
"It's not a surprise, because I wrote him and he told me it wasn't looking good at all," he said.
"I kind of saw it coming. But obviously when it's official, it's disappointing for tennis, there's no doubt about it."
Federer also expressed his concern over Nadal's long-term fitness.
"I would love to have him in the draw," stated the 31-year-old. "With 12 days before the Open you figure he might still have time to fix what he has to fix to get ready.
"If he pulls out that early before the Open, it must be something serious. That's what is sort of scary. There is obviously the whole debate going on if he is going come back for this year.
"I hope in hindsight this is a very smart decision by him. But it's obviously a big blow and disappointing news for the tennis world."
The US gets underway in New York on August 27.