President Nicolas Maduro presented an altered version during his weekly television show on Sunday.
Maduro has called for a vote on July 30 to elect a special assembly that is to draft a new constitution.
"Our call to the "Constituent Assembly" only seeks to unite the country".
"Despacito" - a racy track full of sexual innuendo which features Puerto Rican rapper Daddy Yankee - went viral soon after its release in January, and found an even wider audience in April when pop celebrity Justin Bieber sang in a remix.
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Venezuelans protest Maduro's plan to rewrite constitution
The 23-year-old was seen with blood gushing from cuts on the left side of his face. The opposition said 85 per cent of the country joined the strike.
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Luis Fonsi responded angrily on social media: "At no point was I asked, nor did I authorise, the use or the change in lyrics of Despacito for political means, and much less so in the middle of the deplorable situation experienced by Venezuela, a country I love so much".
"My music is for everyone to listen to and enjoy, not to be used as propaganda that intends to manipulate the will of a people who are screaming for their liberty and a better future", Fonsi said in a message posted to Instagram.
The previous song to hold the title was Bieber's single "Sorry" and its associated remixes, which to date have accumulated 4.38 billion plays since 2015. "You dictatorial regime is a mockery, not only for my Venezuelan brothers, but also for the whole world".
"What can you expect from a person who has robbed the lives of so many young people filled with dreams?" Those in favor of rewriting the constitution, however, say the president is simply hoping to restore peace in his fractured country.
But opposition leaders fear that the president's move towards a constitutional shake-up would delay this year's regional elections and next year's presidential election.