The two Spanish powers meet at the Wanda Metropolitano after a busy week of World Cup qualifying.
Barcelona face a tricky away tie at the Wanda Metropolitano stadium as Atletico Madrid encounter their first difficult test at their new home ground in La Liga.
They welcome a side who are unbeaten in the league, winning all seven under new coach Ernesto Valverde.
Meanwhile, Diego Simeone will be looking for his side to bounce back from a difficult couple of fixtures which took place before the international break, with a disappointing stalemate away to Leganes following a one-sided defeat at home to Chelsea in the Champions League.
With Argentina on the brink of not booking a World Cup place, talisman Lionel Messi sent his team on their way to Russia by scoring a breathtaking hat-trick.
All eyes will be on the amazing forward this weekend to see if he can keep up his rich vein of form.
In this fixture last year in La Liga, a closely contested tie was settled with only four minutes to go, with Barcelona briefly going top of the table with a last-ditch winner from Messi.
As the visitors dominated the game with the vast majority of possession, Simeone looked like he pulled off a tactical masterclass by keeping the Catalan giants at bay, setting his team up to defend from the start.
It took more than an hour for the match to come to live, but when it did fireworks ensued with Rafinha taking the lead for Barca in a much deserved opening goal.
It didn't take long for the hosts to reply, as key defender Diego Godin came up with the goods when it mattered with a thumping header within five minutes of going behind.
In the dying embers of the game, Messi showed why he is one of the greatest of all time, reacting quickest in a congested box to poke home and give his side a vital three points.
With seven wins from seven at the start of the La Liga campaign, conceding only two while smashing in 23, Barcelona have shown their rivals for the 2017/18 season that they are not to be messed with.
Can they keep the record going against Atletico? It will be difficult in their brand new stadium, where they will be keen to not be embarrassed in front of an expectant crowd.
Atletico will be looking to turn over a new leaf after a relatively poor September by their standards. Although they had many chances against Leganes, they couldn't make them pay and managed only a poor 0-0 result.
Against Chelsea, they kept the ball well but were outclassed by a much stronger side. With three draws and four wins, they need to turn those ties into victories to keep in touch with Barcelona at the top.
Defender Lucas Hernandez has now returned to training and could feature, but it looks like important left back Filipe Luis could miss the match after suffering a hamstring injury when he faced former side Chelsea in the Champions League.
Croatian defender Sime Vrsaljko could also be absent after picking up a knock on international duty.
Meanwhile, Barcelona are looking a bit short in terms of attacking numbers, with a few midfielders sidelined with injuries.
Luis Suarez could miss the match after picking up a knee injury on international duty with Uruguay, with his potential absence a huge blow to Valverde and the team.
Ousmane Dembélé and Andres Iniesta are also likely misses with hamstring injuries, although club captain Iniesta insists he might be able to return in time for the Atletico visit.
Summer signing Dembele could be out of action until after the winter break.
Predicted Atletico Madrid XI: Oblak, Juanfran, Savic, Godin, Vrsaljko, Saul, Thomas, Koke, Carrasco, Griezmann, Correa
Predicted Barcelona XI: Ter Stegen, Semedo, Pique, Umtiti, Alba, Busquets, Rakitic, Gomes, Messi, Deulofeu, Paulinho.
Many will back Barcelona, due to their exceptional form and superb record away at Atletico.
However, with a number of key players out injured for Barca, Simeone might believe this could be a chance to nick three points and upset the balance in the league.
After all, as a team they are only six points off the top and have the tactical knowhow to win the league.
Prediction: Atletico Madrid 1-1 Barcelona