He was withdrawn after 26 minutes during their 4-2 win over Sevilla at the Camp Nou on Saturday night, after injuring his shoulder.
The club’s medical team confirmed he is expected to be out for three weeks with a fractured arm, missing the Champions League double header against Inter Milan, La Liga games against Rayo Vallecano and Real Betis and a Copa del Rey tie against Cultural Leonesa, as well as the crunch tie with Real.
He was replaced in the Sevilla game by French international Ousmane Dembele, and he is set to start in place of Messi this weekend.
Dembele, who signed from Borussia Dortmund in a £96m deal last summer, started in Barcelona’s first seven La Liga games of the season – however he only completed 90 minutes once.
He has only appeared from the bench in their last two games, as Ernesto Valverde has brought summer signing Arthur into the starting XI, and restructured his midfield accordingly.
Dembele’s start to the season looked promising, with winning goals in the Spanish Super Cup final against Sevilla and in La Liga away at Real Sociedad, but injuries and dips in form have disrupted him.
He did not play in last season’s El Clasico ties, only named as an unused substitute for one of them, but on Sunday he faces his biggest test as a Barcelona player.
In the first El Clasico without either Messi or Cristiano Ronaldo since 2007, there is a sense that a new young star will have to step forward in this tie.
Real Madrid will be looking to Marco Asensio, but for the home side, Dembele will be charged will going some way to fill the creative void left by Messi.
If he takes this opportunity with both hands, he will remain in the side in Messi’s absence, and make a strong case to start over someone else upon the Argentine’s return.
If he does not, he will face more questions, and the possibility of other players moving ahead in the pecking order.
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