Cristiano Ronaldo, of course, has departed for Juventus after a nine-year stay in Madrid that yielded 450 goals and 15 trophies including four Champions League crowns.
And now Lionel Messi is absent too, with Barca's talisman sidelined after breaking his arm in last weekend's 4-2 victory against Sevilla - a result that sent the reigning champions top of the table and gives them the chance to move seven points clear of struggling Real today.
It will be the first Clasico featuring neither Messi nor Ronaldo since December 2007, when Real triumphed with a solitary goal from Julio Baptista in a game featuring other blasts from the past such as Deco, Gianluca Zambrotta, Gabriel Heinze and Ruud van Nistelrooy.
Since then, Messi and Ronaldo have been the brightest of stars in the galaxy of world-class talent that is El Clasico: Messi is the fixture's all-time leading scorer (26 goals) and assister (14), while Ronaldo holds the record for the most consecutive Clasicos with a goal (six games, all in 2012).
So how will Barca cope with Messi's sudden absence? How will Real overcome their post-Ronaldo hangover? How will the pair's absence affect the wider pattern of the game? AGENCIES