Defending champion Rafael Nadal has decided not to play the US Open later this month because the coronavirus pandemic is “not under control”.
Spanish world number two Nadal, 34, has not entered the tournament, which takes place in New York from 31 August.
“The health situation is very complicated around the world with cases increasing and flare-ups,” said Nadal.
Serbia’s Novak Djokovic leads the men’s entry list, while American great Serena Williams has indicated she will play.
Nadal added: “This is a decision I never wanted to take but I have decided to follow my heart this time and for the time being I rather not travel.”
The United States Tennis Association (USTA) is hosting a double tournament at Flushing Meadows, having moved the Cincinnati Masters to New York.
The event will staged at the Billie Jean King Tennis Centre from 22 August, with the US Open taking place immediately afterwards.
Both tournaments will be held without fans and players will have to follow strict measures.
The USTA measures within the safety bubble include regular testing, mitigation measures and increased sanitisation. The organisation said on Friday it was confident the health and safety of everyone involved in the tournaments remained “on track”.
While the WTA Tour resumed in Palermo this week, the Cincinnati-US Open double header will be the first ATP events since March.
“We know that the reduced tennis calendar is barbaric this year after four months stopped with no play,” added Nadal, who will miss a Grand Slam for the first time since Wimbledon in 2016.
No Nadal or Federer - who is playing?
Nadal’s great rival Roger Federer will also be absent from the US Open, with the 38-year-old Swiss recovering from knee surgery.
Australian Ashleigh Barty, the women’s world number one, said last week she did not want to play, meaning Romania’s world number two Simona Halep leads the entry list.
Defending women’s champion Bianca Andreescu has also entered.
The entry list is not a guarantee that those on it will play the Grand Slam tournament, with many players likely to make a final decision over the next few weeks.
Britain’s three-time Grand Slam champion Andy Murray does plan to play at Flushing Meadows, although the world number 129 will need a wildcard if he is not promoted from the alternate list.
British number ones Johanna Konta and Dan Evans have entered the tournament through their rankings, as have compatriots Heather Watson, Kyle Edmund and Cameron Norrie.