The fixture had to be postponed in October due to violent demonstrations and there are renewed fears of unrest breaking out around Camp Nou, where Barça and Madrid will tussle for top spot in La Liga.
Around 3,000 security personnel will be deployed at the stadium and both teams have been instructed to gather at the Hotel Princesa Sofia at midday (1100 GMT) on Wednesday, eight hours before kick-off.
The players, coaching staff and referees will then travel together to the ground around two hours ahead of the match.
It means Madrid will be in a different place to their usual base in the city while Barcelona will arrive earlier than normal for a home match.
“It is a small change, but not very significant. When we play away, we are also in a hotel. It is not a big problem,” said Barcelona's coach Ernesto Valverde on Tuesday.
Madrid coach Zinedine Zidane described the arrangements as “something different but the rules are the rules”.
Barcelona also issued a statement on Tuesday night to fans planning to attend the game, advising supporters to use public transport, allow plenty of time and warning of “exhaustive security checks” at entrances to the stadium.
Barça called for calm around the fixture, asking fans “to come to the game at Camp Nou on Wednesday to support the team”.
“The game between Barça and Real Madrid is a festival of football and yet it is without doubt also compatible with a civil and peaceful demonstration of opinion, given the exceptional circumstances faced in Catalonia in recent times,” the statement read.
Violent protests broke out in Catalonia in October after nine separatist leaders were sentenced to heavy prison sentences for their involvement in the independence referendum of 2017.
The Clasico was supposed to be played on October 26 but the RFEF decided to postpone “due to exceptional causes”.
Vine a veure el clàssic! ? ⚽
Dimecres es necessitaran milers de persones per fer l’acció. A més, tothom que vingui estarà convidat a veure el partit. I com a tots els partits, cal portar ràdio, aigua i entrepà! ? ?#LaForçaDeLaGent ? pic.twitter.com/xg5XfUXq5q
— Tsunami Democràtic (@tsunami_dem) December 16, 2019
Democratic Tsunami, the protest group advocating another independence referendum for Catalonia, has called publicly for its supporters to gather at Barcelona's Camp Nou stadium from four hours before the 1900 GMT kick-off.
“Football has to be for everyone, all over the world,” said Valverde. “People should be able to express themselves freely tomorrow, that is what we ask, but that there is respect for everyone. I believe that is the right
Meetings have taken place between the police, clubs and the Spanish Football Federation (RFEF) to ensure the safe arrival of the two squads and referees, as well as the nearly 100,000 fans expected to attend.
As well as the massive security presence in Barcelona, the numbers of private security staff in the stands will also be increased to reduce the threat of pitch invasions that could interrupt the game.
“The operation will ensure that the Clasico is played normally,” said the chief commissioner of the Catalan regional police Eugeni Sallent.
Democratic Tsunami hopes to transmit its message — 'Spain, sit and talk' — through one of the world's most famous football matches, which has an estimated global audience of 650 million.
Barcelona have historically had a close association with Catalan nationalism, with Camp Nou routinely used as a setting for flags, banners and chants in support of the cause.
“We know we are living in a complex social and political situation but I am convinced that it is compatible with playing a football match,” said the club's president Josep Maria Bartomeu last week.
Barcelona could also suffer the consequences of any altercations or interruptions during the fixture.
At a meeting in Madrid last week, the RFEF warned it “will apply the regulations in force,” which range from heavy economic sanctions to the closure of Camp Nou to supporters.