Real Madrid have never played against a Swedish side, while Malmö has only played and lost against Atlético.
So sports commentators are already rushing to preview the unique fixture at the Swedbank Stadium in southern Sweden.
"Shoestring Swedes hope to upset mighty Madrid," wrote the Reuters news agency on Tuesday.
Eurosport commented: "It's a David vs Goliath Champions League clash - and we all love those."
It added: "Either Cristiano Ronaldo and company put on a glorious exhibition, or Malmö keep us on the edge of our seats with an exceptional performance to maintain an unexpected scoreline for all or much of the contest. It's a win-win!"
Malmö, the Swedish champions, are competing in the UEFA Champions League group stage for a second successive season having made their debut in 2014/15.
Meanwhile Real Madrid have won 13 of their last 14 Champions League group games.
Their star striker Cristiano Ronaldo is just two goals shy of matching Raul's 323-goal record as Madrid's top goalscorer of all time.
However, he has been made to wait for his historic moment after failing to find the net in La Liga meetings against Granada, Athletic Bilbao and Malaga in the past 10 days.
Rafael Benitez's men have now been held scoreless twice in their opening six La Liga fixtures, but the former Liverpool and Chelsea boss is confident the goals will come for the Spanish legends as they take on the Scandinavians.
"Creating so many chances seems positive to me, but preventing opportunities on the counter-attack is something that we need to correct as well as managing the anxiety at the end of games," he said ahead of the game.
However, he confirmed on Tuesday afternoon that he had not included top players Gareth Bale, James Rodriguez, Sergio Ramos or Pepe in his 20-man squad for the clash with Malmö.
With Real having won their opening encounter in Group A 4-0 against Shakhtar Donetsk, the manager appeared not to want to risk any of his star names in Sweden.
Malmö's goalie Johan Wiland. Photo: Andreas Hillergren/TT
Malmö goalkeeper Johan Wiland is the man tasked with the unenviable job of stopping a Madrid side desperate to make amends for the weekend, but the 34-year-old is relishing the opportunity to face the world's best.
"I love games where I have a lot to do," he told Malmö FF's website.
"You have to make the best of it. It also feels special when the Champions League song goes on. I think you can ask Ronaldo and he would say the same thing.
"You have to go out there and enjoy it. I have told all of the players that, but we should also do the job. We are a very good football team and we have a chance."