Josep Borrell lashed out at Catalonian secessionists and accused them of “deceiving” their supporters.
The former European Parliament president said the campaign for an independent state was based on lies and said any new state would struggle outside of Spain.
He said: “How many times do we have to repeat the same thing? How many times do European authorities have to say that a new state would be outside the European Union? It would not have any international support.
“In what world do you think you live? Do you think someone is going to support them? Stop deceiving people.”
He also lashed out at a group of Catalan secessionists who were accused of hijacking a memorial event for victims of the Barcelona terror attack victims.
Mr Borrell said campaigners had exploited the event and also heckled Spanish officials in attendance.
He said: “I found it regrettable that some of the attendees converted what was a unitary demonstration against terrorism and support for the victims… in a demonstration in favour of independence.
“The shouts to the Spanish head of state and the booing of a minority are reproachable and condemnable behaviour.”
Mr Borrell raged at the “demonstrations that have occurred in Europe after there have been terrorist attacks, where everyone has put aside their political differences”.
The ex-eurocrat added: “It was a very reprehensible attitude that makes me feel ashamed. They turned that into a manifestation of their points of view, forgetting the dead that were about to be buried.”
This is not the first time Mr Borrell has lashed out at Catalonian attempts to secure independence.
Earlier this year the Spanish politician said: “Catalonia has no right to self-determination because it is neither a colony nor militarily occupied nor denied the rights of national minorities, which are the only cases for which the UN recognises this right, despite the fact that the national-independentistas do not want to find out.”
He accused leaders of purposefully fostering a sense of other within the region.
Mr Borrell said: “The nationalist governments of Catalonia have systematically and consistently endeavoured to create, through the educational system and the public media, that feeling of identification with the Catalan nation, whose membership of the Spanish State was a historic accident determined by the misfortune of arms.”