Chanting 'Independence' and 'Free political prisoners', several thousand Catalan protesters gathered near Barcelona's Camp Nou stadium on Wednesday hours before the home side faced rivals Real Madrid in Spain's most high-profile match.
Despite a heavy police presence, some protesters blocked a major avenue near the stadium, disrupting traffic ahead of the game which finished 0-0.
Minutes before the match began, Catalan police broke up fighting that flared between some Barcelona fans and pro-independence protestors, detaining one person for throwing projectiles at them.
As the second half got underway, masked demonstrators broke down an exterior fence in a failed attempt to gain entry to the stadium, a police spokesman said.
The group set fire to waste containers to create a barricade before several vans of police arrived to disperse the crowd, Reuters TV footage showed.
The La Liga game, known as 'El Clasico', had initially been scheduled to occur two months ago. However, it was postponed due to security concerns amid unrest in the wealthy north eastern region after Spain's supreme court in October sentenced nine Catalan separatist leaders to up to 13 years in prison.
Wednesday's protest was called by a secretive Catalan protest group Democratic Tsunami, which says it favours peaceful civic disobedience. The group's main goals are to get Spain to negotiate on Catalonia's right to self-determination and to achieve freedom for the jailed separatists.
Many protesters carried banners that read 'Spain, sit and talk'. Democratic Tsunami tweeted it would distribute 100,000 of those banners to the people attending the game. It also told them to bring inflatable balls and to write on them a 'message for the world'.
Democratic Tsunami, which organised mass protests at Barcelona's airport in October and blocked a major highway, said it did not wish to blockade or suspend the match.
Authorities assembled a 3,000-strong force of public and private security officers to guarantee the match would not be disrupted, but declined to say how that compared to other 'El Clasico' games.
The Spanish central government sent around 500 additional anti-riot police to Barcelona who would only intervene if the Catalan police asked for their help, a national police spokesman said.
Protesting in front of a hotel near the stadium where both teams were resting, pro-independence voter Marta Canaves, 53, said the venue was a "great place to make visible to the rest of the world" the situation in Catalonia.
"We want to be heard and to vote," added her friend Emma Castells, 55, referring to separatist demands to hold a referendum on independence.