The poll will measure the popularity of a key plank in Prime Minister Silvio Berlusconi's policy platform.
A month after winning the last election, in September 2008, Berlusconi promised a new national energy plan involving "the start of nuclear energy production".
Opinion polls suggest a strong majority of Italians oppose reintroducing nuclear energy. But unless more than half of all eligible voters participate, the ballot will not count.
"We are campaigning in Germany, Switzerland, France and Belgium for those Italians living there who have a right to participate in this referendum to get out and vote," German MEP Rebecca Harms, co-president of the Greens/European Free Alliance group in the European Parliament, told EurActiv.
But concerns remain high that Germany's decision could usher in more coal, gas and imported nuclear energy as a replacement.
EurActiv understands that, in a recent phone conversation, German Environment Minister Norbert Röttgen reassured EU Climate Action Commissioner Connie Hedegaard that renewables would be speedily mobilised to fill any gaps in the German energy grid.
In an emailed statement, Hedegaard told EurActiv: "My congratulations to Germany for sticking to its 40% CO2 reduction target for 2020."
"This will be reached through energy savings, enhanced renewables and by replacing old coal-fired stations with new gas-fired plants."
The Italian vote may help determine whether such trends gain momentum across the continent, with countries such as Poland already considering similar ballots.
According to Harms, an Italian decision not to go nuclear is likely to be felt first in the partially-European Turkey, which recently angered Bulgarians with plans to build a nuclear reactor on its Black Sea coast.
"Although it is not an EU member state, Italy and Turkey have very similar earthquake problems and this poses special risks," she told EurActiv.
"Because the safety of the country and the continent is at stake, we are especially asking Italians not to go nuclear."