Nine people were arrested after clashes broke out between police and protesters outside Camp Nou on Wednesday as Barcelona and Real Madrid played out a goalless draw in La Liga.
The incidents followed a day of demonstrations around the stadium which had been called to coincide with the Clasico to protest the imprisonment of Catalan politicians in October.
Thousands of people gathered before the match to protest peacefully and the game between Spain's top two got underway without any complications.
However, as the match was played, protesters clashed with Barca ultra group the Boixos Nois and later with police. Authorities said late Wednesday night that 46 injuries were recorded, with eight people taken to a local hospital.
A number of bins were also set on fire outside Camp Nou, with the smoke and smell drifting into the stadium during the final 20 minutes of the game. A continual announcement over the public announcement system told fans that they would only be able to leave through exits on one side of the ground due to security concerns.
Over 3,000 police officers and private security personnel had been drafted in to cover the game due to the planned protests. It represented the largest security operation in Clasico history.
Barca and Madrid had also been forced to spend the afternoon at the same hotel before being escorted to the stadium.
Tsunami Democratic, a Catalan protest group advocating for a self-determination referendum, had called the demonstrations to bring wider media coverage to the political situation in the region.
The group has organised a number of protests since nine Catalan politicians and civic leaders were jailed in October for their role in organising a unilateral referendum in 2017. They are calling for dialogue between Spain and Catalonia.
Thousands of banners carrying the slogan "Spain, sit and talk" were handed out to the 100,000 supporters attending Wednesday's game and they were held up at various stages of the match. A huge banner with the same message was also unfurled prior to kick off.
The fixture, which was originally called off on Oct. 26 due to fears over security following protests, was briefly halted in the second half when hundreds of beach balls were thrown on the pitch.
On the pitch, Barca and Madrid played out a goalless draw which left both teams locked on 36 points at the top of the table after 17 games.