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Voting in two regions of eastern Ukraine opened Sunday, as pro-Russian separatists called for a split from the rest of the country.
The ballots seek approval to declare sovereign the so-called people's republics in the Donetsk and Luhansk regions, where armed pro-Russia insurgents have taken control of government buildings and clashed with Ukrainian military troops.
The United States has called the referenda "illegal" and "an attempt to create further division and disorder."
"If these referenda go forward, they will violate international law and the territorial integrity of Ukraine. The United States will not recognize the results of these illegal referenda," State Department spokeswoman Jen Psaki said in a statement.
The United States will continue supporting the Ukrainian government's efforts to hold a presidential election on May 25, Psaki added.
Ukrainian leader Oleksander Turchinov warned the regions they would be stepping into the abyss if they voted for self-rule.
The vote comes amid increasing violence in east Ukraine.
The Associated Press contributed to this report.