Emergency services are still at the scene looking for more victims. "New victims cannot be ruled out," the services said on their website.
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The cause of the blaze is not yet known.
The injured are two women, aged 22 and 25, and two men, aged 41 and 45, who were all taken to the hospital due to smoke inhalation, the Murcia emergency services website said.
Survivors gathered outside the nightclub described the scene to journalists as emergency services carried out their work
"I think we left (the club) 30 seconds - 1 minute before the alarms went off and all the lights went out the screams saying there was a fire. I was at place at that time where I could get out, but five family members and two friends are missing," an unidentified survivor told Reuters.
"We don't know anything, we are waiting for news to see whether some of our family members have come out alive," said another man at the scene.
The President of the Murcia region posted on X, formerly Twitter, "Worried and dismayed by the news coming from there (Murcia). The emergency services continue working."
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At the time of the incident, emergency services were dispatched, with local firefighters requesting the intervention of the helicopter from the General Directorate of Security and Emergencies, the emergency services said, adding later that ground resources were sufficient to put out the fire.
"The General Director of Security and Emergencies, Ricardo Villalba, is on-site coordinating with the Murcia City Council the necessary means to manage this tragedy," the emergency services said.
"The Vice President and Minister of the Interior, Emergencies and Territorial Planning, Jose Ángel Antelo, is expected to arrive at the site," they added.
Three days of mourning have been declared in the city of Murcia for "those who died in the fire that occurred at the Teatre de Atalayas nightclub", Murcia mayor José Ballesta said on X.
An information area for relatives of the victims was set up in the nearby Palacio de los Deportes, where a team of psychologists will be tasked to provide assistance.
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