Italian Prime Minister Matteo Renzi is preparing for his resignation.
The result plunges the country into political turmoil, but with the European Union already reeling from multiple crises and struggling to overcome anti-establishment forces, many sought to downplay the broader significance of the vote.
EU finance commissioner Pierre Moscovici told reporters in Brussels that he has "full confidence in Italian authorities to manage this situation".
He added: "I'm very confident in the capacity of the eurozone to resist all kind of shocks."
German finance minister Wolfgang Schaeuble said Italy should continue the economic reforms begun by Mr Renzi.
He also said investors should be relaxed about the Italian referendum, which was a domestic issue, and said he saw no grounds for there to be a crisis for the euro currency.
"I think we should see the situation in Italy with a certain calmness," he said, adding: "I think there is no need to talk about a euro crisis."
German foreign minister Frank-Walter Steinmeier, however, said that while the result was "not the end of the world", it was also "not a positive development in the case of the general crisis in Europe".
He said he was watching the developments "with concern"
The markets seemed initially to take Mr Renzi's departure in their stride and appeared to bet against snap elections.
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