Madrid are struggling to adapt to life without Cristiano Ronaldo, who left for Juventus in the summer having led the Blancos attack in stunning style since 2009.
And now Barcelona will also have to soldier on in the absence of their talisman.
Lionel Messi was forced off after just 26 minutes on Saturday when he fell heavily on his right arm during Barca's 4-2 victory over fellow Liga challengers Sevilla.
In typical Messi style, he had already contributed a goal and an assist to the Catalans' efforts before hurting himself, a double salvo that underlines his importance to Ernesto Valverde's team.
And now, with confirmation he will miss three weeks of action with a fracture in the limb, Barca know they must welcome their arch-rivals to Camp Nou without the presence of the record-breaking Argentine wizard.
To find the last time neither Ronaldo nor Messi took part in the Clasico, moreover, one must look all the way back to the end of 2007, a full 11 years.
The Portuguese was still leading the way at Manchester United at that time, while Messi was laid low by a torn thigh muscle once more in the week leading up to the blockbuster match.
Barcelona lined up with Victor Valdes; Eric Abidal, Rafa Marquez, Carles Puyol, Gabriel Milito, Deco, Xavi, Andres Iniesta, Yaya Toure, Ronaldinho and Samuel Eto’o. Madrid's starting XI was Iker Casillas, Gabriel Heinze, Fabio Cannavaro, Sergio Ramos, Pepe, Lassana Diarra, Wesley Sneijder, Julio Baptista, Ruud van Nistelrooy, Raul and Robinho.
In a tight game at Camp Nou, the visitors took the honours thanks to a solitary goal from Julio Baptista, and went on to defend their Liga title by finishing eight points clear of nearest challengers Villarreal and a full 18 points ahead of Barca, who were relegated to third.
Indeed, Barcelona's fortunes in the Clasico without their No. 10 have been positively cursed since Messi burst onto the scene in 2004.
Messi has missed just two Clasicos in the intervening 14 years, neither of which have ended with a Blaugrana win.
On April 1 2006 the youngster was nursing a muscle tear when Frank Rijkaard's men drew 1-1 with Madrid at Camp Nou, on their way to a Liga and Champions League double.
With 26 goals Messi is by far the highest scorer in Clasico history, outstripping both Alfredo Di Stefano and Ronaldo (18 goals each).
And news that he will not be available on Sunday has hit hard at Camp Nou, while it is clear that on the other side of Spanish football's great divide life without Ronaldo continues to disappoint.