"Stop this escalation of radicalism and disobedience once and for all," Mariano Rajoy said in a televised statement as protesters remained in the centre of the Mediterranean seaside city after a day-long demonstration that headed into the night.
"There is still time to avoid bigger problems."
Shouting "we will vote," independence supporters started their gathering on Wednesday morning after police detained 14 Catalan government officials, raising tensions as Madrid pulls out the stops to prevent regional separatist leaders from holding the vote on October 1.
Over in Madrid, hundreds of supporters of the referendum gathered in solidarity in Puerta del Sol square, which hosted scores of anti-austerity protests during the Spanish economic crisis.
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Among those arrested by the Guardia Civil police was Josep Maria Jove, secretary general of economic affairs and Catalonia's deputy vice president, a regional government spokesman said.
The others work in various Catalan government departments and are suspects in a probe into "disobedience, misfeasance and embezzlement", the High Court in Catalonia said.
Catalan President Carles Puigdemont condemned the "totalitarian and undemocratic attitude of the Spanish state."
He accused Madrid of imposing a "de facto" state of emergency to stop the referendum.
In central Barcelona, several thousand people were still gathered in front of Jove's office late this evening, some draped in red and yellow Catalan flags.
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