The State Department denial followed an accusation by Venezuelan Foreign Minister Elias Jaua that opposition leaders supporting protests against the rule of President Nicolas Maduro the past two weeks were financed and orchestrated by Washington and "U.S. institutions."
"We ... see a lot of conspiracy theories or rumors out there in the press about how the U.S. is interested in influencing the domestic political situation in Venezuela, which is absolutely not true," State Department spokeswoman Marie Harf told reporters.
"We've made clear that we're open to having a constructive relationship with the government of Venezuela.
"Quite frankly ... we have not seen that reciprocated."
Maduro and his ministers blame the United States for many of Venezuela's growing ills, including rampant crime, widespread food shortages and a fast-falling currency.
They paint Washington as an imperial enemy bent on destroying the economy, crushing the regime and wrecking the socialist-inspired revolution of Maduro predecessor Hugo Chavez, who died of cancer in March 2013.
Jaua told Venezuela's teleSUR network Thursday key opposition leader Leopoldo Lopez was carrying out Washington's orders when pro- and anti-government violence erupted Wednesday that left three people shot to death, all from behind, and 66 wounded.
It was not immediately clear who the gunmen were but they were believed to be pro-government vigilantes, Britain's Independent newspaper reported.
At least 69 people arrested, the Interior Ministry said.
The violence started an hour after the end of a peaceful anti-government protest of about 10,000 people in downtown Caracas, the capital, calling for the release of student activists detained during similar protests elsewhere in Venezuela last week.
The country has been gripped the past two weeks by increasingly heated protests calling for Maduro, a 51-year-old former bus driver, to resign and complaining about economic hardships, soaring crime and rampant corruption.
Jaua's accusations came as the government issued an arrest warrant for Lopez, 42, a Harvard-educated former mayor of a Caracas district who Chavez banned from running for public office until this year.
Lopez is the great-great-grand nephew of Venezuelan revolutionary figure Simon Bolivar. Chavez invoked, and now Maduro points to, Bolivar as a modern-day symbol of independence from presumed outside oppression.
The arrest warrant accuses Lopez of crimes including homicide, terrorism, conspiracy, instigating crime, public intimidation and setting a public building on fire, Venezuelan newspaper El Universal reported.
Lopez, leader of the opposition party Popular Will, told the crowd Wednesday, "All of these problems -- shortages, inflation, insecurity, the lack of opportunities -- have a single culprit: the government," the Independent said.
The government also sought the arrest of a former high-ranking naval officer and a former Venezuelan ambassador to Colombia, who Maduro said on television were recorded earlier predicting the protests would end in bloodshed.
Lopez was studying the details of the arrest warrant with his lawyers, ally Carlos Vecchio told the Wall Street Journal.