The opposition Socialist party called the vote because it wants the government to reverse its decision not to build a new plant at Belene.
The first referendum in Bulgaria’s post-Communist history has polarized opinion and is seen as a precursor of general elections later this year.
The referendum would only be valid if at least 60% of the electorate votes.
The government says it supports the provision of nuclear power from an existing plant at Kozloduy, but that it does not have the 10 billion euros it says would be needed to build a new plant.
Prime Minister Boyko Borisov told local media that this would remain the case even if Bulgarians voted in favor of a new nuclear plant.
Bulgaria had to close four of its old reactors at Kozloduy as a precondition for its 2007 EU membership.
The government froze plans to finish the plant at Belene last year, when work at the site on the southern bank of the River Danube was already well under way.
The Socialists are seen as closely linked to the Belene project, having granted a construction contract for the plant to Russian state company Atomstroyexport in 2008.
They say Belene would now cost 4-6 billion euros to complete, and would lower electricity costs for consumers.
Environmentalists had opposed the plant, which had first been proposed when Bulgaria was under communist rule.
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