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The 20-time grand slam singles champion has not played since losing to Stefanos Tsitsipas in the quarter-finals of the Australian Open in February.
Nadal pulled out of the Rotterdam Open and turned down a wildcard for the Dubai Tennis Championships due to a persistent back problem.
Sad to announce that I won’t be playing in Miami, a city that I love. I need to fully recover and get ready for the clay court season in Europe. Special message to my fans in the US and in particular to the great Spanish speaking community FL who always give me a great support!💪🏻— Rafa Nadal (@RafaelNadal) March 16, 2021
The world number three, who has never won the title in Miami, wants to prioritise his recovery ahead of the beginning of the clay-court swing in April.
Writing on Twitter on Tuesday, he said: "Sad to announce that I won't be playing in Miami, a city that I love.
"I need to fully recover and get ready for the clay-court season in Europe. Special message to my fans in the US and in particular to the great Spanish-speaking community FL who always give me a great support!"
Nadal follows long-time rival Roger Federer in withdrawing from the tournament, the Swiss great choosing to focus on training after only returning to the Tour from a 14-month absence at the Qatar Open.
Federer is the reigning champion in Miami, having beaten 2018 winner John Isner in the final two years ago. The 2020 tournament was cancelled due to coronavirus concerns.