The American said she was “disappointed” to miss playing in her home tournament because of "recent oral surgery".

Her withdrawal comes after Serbia’s Novak Djokovic confirmed he would not be travelling to America due to COVID-19 restrictions and a desire to spend more time with his family.

Spain’s Rafael Nadal, Switzerland’s Roger Federer and Austria’s Dominic Thiem have also opted to skip the hard-court event to focus on preparations for the clay-court season.

"We will certainly miss having Serena at this year’s tournament and I know it was a very difficult decision for her," said tournament director James Blake.

"She has won the Miami Open more than any player in history, has a home here in South Florida and is always a fan favourite.

"We hope she is back on the court soon and look forward to welcoming her back here next year."

The Miami Open is a premier event for both the Women’s Tennis Association (WTA) and the Association of Tennis Professionals (ATP).

The tournament, which began with qualifying today, also returns after it was cancelled last year because of the coronavirus pandemic.

Men’s defending champion Federer will not be there but Australia’s Ashleigh Barty, who won the women’s singles title in 2019, is due to play in her first tournament outside of Australia since the Qatar Total Open in February 2020.

The women’s main draw features 19 of the WTA’s top 20 including Australian Open champion and world number two Naomi Osaka of Japan.

Romania’s Simona Halep, American Sofia Kenin and Canadian Bianca Andreescu, who are ranked third, fourth and ninth in the world respectively, are also set to return to action for the first time since departing Australia.

Three-time Miami Open champion Victoria Azarenka of Belarus is seeded at number 14 and is a potential last-16 opponent for Barty.

Men’s world number two Daniil Medvedev will hope to make the most of the absence of Djokovic, Nadal, Federer and Thiem as he bids to clinch the first ATP Masters 1000 event of the year.

The Russian, who reached the final of the Australian Open, is one of six players inside the world’s top 10 that will be in action in South Florida.

The three-time Masters 1000 winner will be joined Greece’s Stefanos Tsitsipas, Germany’s Alexander Zverev, Russia’s Andrey Rublev, Argentina’s Diego Schwartzman and Italy’s Matteo Berrettini.

The tournament has awarded a wildcard to former world number one Andy Murray of Britain, as well as rising talents including Spain’s Carlos Alcaraz, American Michael Mmoh, Frenchman Hugo Gaston and Britain’s Jack Draper.

Due to COVID-19 restrictions, just 750 fans will be allowed on site per session with capacity on the 5,000-seater showcase court limited to 15 per cent.

The top 32 seeds receive a first round bye, with the main draw due to begin tomorrow.