Ho took office in December 2019, weeks before the first coronavirus case was recorded in Macau, and his tenure has been marked by efforts to bolster the casino hub's pandemic-hit economy.
His administration had stressed the need to diversify the Chinese special administrative region's casino-driven economy, in line with development plans laid out by President Xi Jinping.
Ho, 67, said in a statement Wednesday he has "profound feelings for Macau and have done my utmost for Macau's development".
"But due to the fact that my health has not been fully restored, for the sake of Macau's long-term development and from the perspective of the overall situation, I have decided not to participate in the election for the sixth-term Chief Executive," he said.
Ho, who ran unopposed in 2019, will conclude his five-year term in December. He thanked the central government and all sectors of Macau "for their full trust and steadfast support".
Questions were raised about his political future after he took a break in June for more than a month.
Macau's leadership race will be held on October 13, the government announced last week.
Only around 400 pro-establishment figures, out of the city's population of 700,000, are eligible to cast ballots in the election.
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