Atletico will be looking for their first league win over Barcelona since February 2010 when they host the Spanish champions.
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.
Atletico have had their problems this season, but they have suffered just one defeat and are right on Barcelona's tails ahead of their match-up this weekend.
Both teams have injury problems ahead of the fixture, but some of the world's biggest stars will be on display at the Wanda Metropolitano.
Here, Sports Mole selects the best team from both squads, using only players available for this weekend's match.
Two of the best goalkeepers in European football will be on display this weekend, and there is no question that Marc-Andre ter Stegen has made big strides forward over the last 12 months. It is difficult to select the German in this XI, however, when considering the presence of Jan Oblak.
While Ter Stegen has conceded 18 La Liga goals and kept just two clean sheets this season, Oblak has shipped just eight and managed six shutouts. The 25-year-old is perhaps the outstanding goalkeeper in world football alongside David de Gea, and it is just not possible to leave him out of this team.
Diego Godin would have been an absolute certainty had he been fit, but the Uruguay international will miss the match with a thigh problem. Atletico teammate Lucas Hernandez is also seen as a doubt, but the Frenchman should pass a late fitness test to start.
Jordi Alba has posted eight assists in 17 appearances this season, however, and his presence means that Lucas switches to right-back for the purposes of this XI. Barcelona teammate Gerard Pique also gets the nod, while Samuel Umtiti is back from a knee problem and deserves a position due to his outstanding form during the 2018-19 campaign.
The midfield is a difficult one when considering that a number of players are seen as doubts. Ivan Rakitic will definitely miss out for Barcelona, while Koke and Thomas Lemar are expected to be unavailable for Atletico. World-class Sergio Busquets is an absolute no-brainer, while Saul Niguez has to start having developed into one of the finest midfielders in European football.
Philippe Coutinho could yet miss out for Barcelona, but the Brazilian has trained this week after recovering from a hamstring problem, and therefore he makes the XI in a deeper midfield role.
Lionel Messi and Luis Suarez take two of the three positions in attack. Messi capped his return from a fractured arm with a brace against Real Betis last time out and now has 14 goals in 13 games this season. Suarez, meanwhile, has managed nine strikes in 12 La Liga fixtures during the 2018-19 campaign.
The other spot goes to Antoine Griezmann. The Frenchman has not quite been himself at club level this season, managing just three La Liga goals. He has struck three times in the Champions League, however, and has to be selected.
Diego Costa has recovered from a foot injury to make himself available this weekend. The Spain international has struggled with a number of issues since February, however, and is without a goal in his last 18 league appearances. Indeed, not since February 25 has the forward netted a top-flight goal, while he has also never been on the scoresheet against Barcelona.