He first battled it when the pandemic first took its hold in March 2020, along with Prince William, and the royals have since received a full round of COVID-19 vaccinations.
Last Thursday, he had to cancel a planned event to mark the 70th anniversary of the Queen's accession.
"This morning The Prince of Wales has tested positive for COVID-19 and is now self-isolating," Clarence House announced in a statement on Twitter.
"HRH is deeply disappointed not to be able to attend today's events in Winchester and will look to reschedule his visit as soon as possible."
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Although his wife Camilla, Duchess of Cornwall, tested negative and continued to carry out several royal engagements, as allowed under government guidelines, four days later, it was revealed that she has contracted the virus.
"Her Royal Highness, The Duchess of Cornwall, has tested positive for COVID-19 and is self-isolating," Clarence House said in a statement.
"We continue to follow government guidelines."
This article first appeared on our sister site, Now To Love.