Busquets suffered an ankle injury in Barcelona's King's Cup victory over Villarreal at the start of March and has missed their last three games.
"The first team player Sergio Busquets has been passed fit," said a club statement.
The home-grown player is a stalwart of Luis Enrique's side providing cover in midfield for Barca's more creative players but it was unclear whether he will start the El Clasico.
If he was only fit for the bench then Javier Mascherano will be the logical replacement to fulfil the role which he did successfully in Barcelona's Champions League victory over Manchester City last Wednesday.
Barca are hoping for a win over Real which will send them four points clear at the top of the table.
(Editing by Sudipto Ganguly)
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