Lionel Messi's return to action was scheduled for the first El Clasico of the season at the Bernabeu. However, Sport is reporting the Argentine's recovery has taken longer than expected and he faces a lengthier spell on the sidelines.
The Spanish publication says the four-time Ballon d'Or winner is not yet at the stage where he can put continual pressure on his knee, meaning he will definitely miss the match with their greatest rivals.
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However, the newspaper also claims that officials at the Camp Nou were never 100% sure the 28-year-old would return in time for the game in the Spanish capital.
The setback also means Messi will miss Argentina's vital 2018 World Cup qualification games with Brazil and Colombia. Tata Martino's men have just one point from their first two fixtures after a home loss to Ecuador and an away stalemate with Paraguay.
Messi's absence is sure to be a huge loss in a game that often boils down to individual moments of brilliance, but the form of Neymar will certainly fill the Catalan faithful with the hope they can take three points off Los Merengues.
The Brazilian has been in scintillating form since his teammate suffered the knee injury against Las Palmas.
He has been directly involved in 12 of Barcelona's last 13 goals and has emphatically stepped up in Messi's absence.
The Camp Nou outfit are currently on a run of five games without defeat - since the 2-1 reverse to Sevilla - and will be hoping to continue their form heading to the Bernabeu.
Will Barcelona be able to win at the Bernabeu without Lionel Messi? Have your say in the comments section below