The blast happened on Friday night at a heavy metal concert inside the Colectiv nightclub, and a large fire broke out.
The death toll was confirmed by Interior Minister Gabriel Oprea and Health Secretary Raed Arafat.
Raed Arafat said 155 people were injured and were now being treated in Bucharest hospitals.
According to local media, fireworks may have been let off inside the club.
More than 500 people may have been inside the club, which was hosting a heavy metal concert.
Romanian President Klaus Iohannis wrote on his Facebook page that he was “deeply grieved by the tragic events that happened this evening in downtown.”
He added: “It is a very sad day for all of us, for our nation and for me personally.”
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