Rafael Nadal's US Open preparations have been thrown into doubt after the world No 4 withdrew from the National Bank Open in Toronto with a lingering left foot injury.

The second seed was scheduled to play South African Lloyd Harris in the second round on Wednesday, but has been replaced in the draw by Spanish compatriot Feliciano Lopez.

The injury already forced the 20-time Grand Slam champion to miss Wimbledon and the Tokyo Olympics, and threatens to derail his US Open campaign.

In announcing his withdrawal, Nadal said the pain of the injury was not allowing him to enjoy being out on the court.

He said: "I have had this issue for a couple of months, as people know.

"Of course, it is not a happy situation after all the success that I had here in Canada, not being able to play this year after missing a year. It’s a tough one, but that’s how it is today. I need to go back and try to find a way to be better again.

"At the end of the day, for me the most important thing is to enjoy playing tennis. Today, with this pain, I am not able to enjoy it, and I really don’t believe that I have the chance to fight for the things that I really need to fight for."

Nadal was able to participate in last week’s Citi Open, but suffered a shock defeat to Harris in the third round.

Nadal added: "I really wanted to play here a lot, but now is the moment to make a decision. This is unfortunately the decision that I have taken, and probably in the next couple of days we are going to know more."

The US Open begins in New York on 30 August.

Injury cut short Serena's Wimbledon challenge

Meanwhile, Serena Williams has withdrawn from the Western & Southern Open in Cincinnati in order to focus on her recovery from the leg injury she suffered at Wimbledon.

The World No 20 was forced to retire from her opening round match against Aliaksandra Sasnovich in June after slipping on a wet Centre Court surface at the All England Club.

In a statement, the 39-year-old said: "Unfortunately, I will not be playing in the Western & Southern Open next week as I am still in recovery from my leg injury at Wimbledon.

"I will miss all of my fans in Cincinnati whom I look forward to seeing every summer. I plan to be back on the court very soon."

The tournament also announced Williams's sister Venus and compatriot Sofia Kenin will not be taking part in the event.

Kenin said she was withdrawing in order to get her body right for the US Open, while the reason for Venus’s withdrawal was not disclosed.

Roger Federer and Novak Djokovic are among a growing number of high-profile players to pull out of the event, which begins on Saturday.