Incredibly, not since a 2-1 success at the Vicente Calderon more than eight years ago have Atletico overcome Barcelona in the league, with the Catalan giants winning 12 of their last 16 top-flight fixtures.
Barcelona currently sit top of La Liga with 24 points from 12 matches, but they are just a single point ahead of third-placed Atletico, who have lost just once in the league this term.
Atletico have also won each of their last four home league fixtures at the Wanda Metropolitano, the last of which was a 3-2 success over Athletic Bilbao.
Here, Sports Mole takes a look at how Diego Simeone's side could line up for the fascinating match in Madrid.
Diego Godin scored a 91st-minute winner for Atletico in their 3-2 success over Bilbao before the international break, but the centre-back will miss out this weekend having suffered a thigh problem against the Basque outfit.
Head coach Simeone will be sweating over the fitness of Lucas Hernandez, Stefan Savic and Jose Gimenez, meanwhile, ahead of the match in Madrid.
Lucas should shake off a hamstring problem to start, while Atletico are also hopeful that Savic will be back from a calf injury, although it is thought that the pair will face late fitness tests. Gimenez, meanwhile, has suffered a series of niggles this season, but should return.
Further forward, Koke and Thomas Lemar are both doubts with muscle and hamstring injuries respectively, which could see Angel Correa, Thomas Partey, Rodri and Saul Niguez continue as the midfield four.
It will also be a big weekend for Diego Costa, meanwhile, as the forward has recovered from a foot injury to make himself available. The Spain international has struggled with a number of issues since February and is without a goal in his last 18 league appearances.
Costa, who has never scored against Barcelona, will be joined by Antoine Griezmann in attack. The Frenchman has also had his issues this season, however, managing just three goals in Spain's top flight.