Blades, 65, wrote on his website on Tuesday that President Nicols Maduro's administration and the opposition were "serving their own agendas" and failing to rein in more than a week of violence between security forces and protesters that has killed at least six people.
The president faces calls to resign from opponents who blame him for the unrest, as well as long-standing problems such as high inflation, crime, and product shortages.
Maduro, the successor of the late Hugo Chavez, said in a national speech on Wednesday that Blades had fallen for foreign propaganda against his government.
"I love him ... but this is an international lobbying campaign to bring artists every day saying something against the revolution, to create the conditions for a (foreign) intervention," said Maduro, who then invited the "Amor y Control" singer to Venezuela.
Blades has yet to take up the offer, but responded to Maduro's accusations on Thursday, saying: "I am not, consciously or otherwise, part of any CIA (U.S. Central Intelligence Agency) plot nor any 'international lobby' aimed at creating bad publicity for any government."
He said the world should try to move beyond using political labels to disparage foes.
"If I criticize someone from the left, then I'm from the CIA. If I criticize someone from the right, I'm a communist. When I criticize the military, I'm 'subversive,'" he wrote.
Blades, a former tourism minister and one-time presidential candidate in Panama, is well-known for the social messages in his song lyrics, such as a swipe at U.S. foreign policy in his hit "Tiburon" ("Shark"). His music can often be heard around Venezuela, especially in poor neighborhoods where the government draws most support.
International celebrities are no stranger to Venezuelan politics. During Chavez's 14-year rule on a platform to put the poor first and end decades of rule by a corrupt elite, he drew high-profile support from Oscar-winning actor Sean Penn, filmmaker Oliver Stone and Argentine soccer star Diego Maradona.
Some of celebrities have transferred their support to Maduro, who calls himself Chavez's "son."
Other musicians have weighed in on Venezuela's political debate in recent days. Singer Madonna posted a photo of Maduro on the social media network Instagram, writing "Fascism is alive and thriving in Venezuela. Apparently Maduro is not familiar with the phrase 'Human Rights'!"
While few celebrities have openly supported Maduro during the current crisis, he enjoys the backing of some local personalities such as TV soap opera stars and singers.
Local classical music conductor Gustavo Dudamel has come under fire from Maduro's critics for going ahead with a series of concerts during the unrest, though Dudamel has not signaled support for either side.