The Catalan club were crowned champions of La Liga last weekend with four games still left to play, after beating Deportivo La Coruna 4-2 in Galicia.
Ernesto Valverde's side are still unbeaten in the Primera Division and will be looking to become the first side since the 1930s in Spain to finish the season without a single league loss.
But Madrid, into the Champions League final after edging out Bayern Munich 4-3 on aggregate on Tuesday, will have other ideas and here, Goal takes a look at everything you need to know ahead of Sunday's Clasico clash at Camp Nou.
Barcelona & Real Madrid injuries
Andres Iniesta has a minor calf problem, but the midfielder should be fit to start what will be his last Clasico clash before leaving Barcelona this summer. Meanwhile, Sergi Samper is still sidelined with a long-term injury.
For Real Madrid, Dani Carvajal is expected to miss out again after picking up an injury in the first leg of Los Blancos' semi-final against Bayern in the Champions League.
Isco, who was also injured in that match, could be fit to return on Sunday, but he is doubtful along with Raphael Varane.
Barcelona & Real Madrid suspensions
Neither of the two teams have any players suspended for the Clasico this weekend.
Barcelona potential starting line-up
With Iniesta set to be fit for Sunday's game, coach Ernesto Valverde is likely to field his strongest side for the Camp Nou clash.
That will see Philippe Coutinho on the right, with Ivan Rakitic alongside Sergio Busquets in central midfield and Iniesta on the left, with Lionel Messi and Luis Suarez in attack.
Sergi Roberto should start at right-back ahead of Nelson Semedo.
Real Madrid potential starting line-up
Apart from pride and the possibility of stopping an unbeaten Barcelona season in La Liga, Real Madrid will still be keen to secure second place in the Primera Division.
Zinedine Zidane's side are 15 points adrift of Barcelona, but only four behind Atletico and they also have a game in hand over their city rivals.
Isco could return to the line-up on Sunday, with Zidane set to choose between him and Gareth Bale in attack, while Casemiro is set to be included in midfield after Mateo Kovacic was preferred from the start against Bayern.
With Varane carrying a knock, Nacho is set to feature in central defence alongside Sergio Ramos, while Zidane will choose between Achraf Hakimi and Lucas Vazquez for the right-back role.
TV channel & kick-off time
Barcelona versus Real Madrid kicks off at 20:45 local time on Sunday and will be broadcast live in the UK (United Kingdom) on Sky Sports Football (from 19:00 BST) and also on Sky Sports Main Event (from 19:30 BST).
In the United States, the game can be watched live on television on beIN SPORTS and kicks off at 14:45 ET.
Best Opta match facts
This will be the 238th Clasico clash in all competitions. Barcelona have won 93 games and Real Madrid have won 95, with 49 games drawn.
Real Madrid have scored 399 goals in the fixture, compared to 387 for Barca. So the next goal for Los Blancos will be their 400th Clasico strike.
Lionel Messi is the all-time top scorer in the Clasico in all competitions (25) and the all-time top scorer in the Clasico in La Liga (17).
Cristiano Ronaldo (17) could equal Alfredo Di Stefano (18) as the all-time Real Madrid top scorer in El Clasico in all competitions.
This will be the first Clasico in which one of the teams has already been crowned champions of La Liga since May 2008. Real Madrid won the title that season and beat Barca 4-1 that day.