Reports on Monday suggested that the Barcelona midfielder was set to pull out of the squad having fractured a finger on his right hand in the 4-0 La Liga win at Eibar this month.
And the Spanish Football Federation confirmed his absence for Thursday's encounter with Italy in Udine, and the contest against Romania at the Cluj Arena three days later.
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"We were aware of the injury and, taking into account recent tests, he has left the group as a precaution to avoid any relapse," Spain team doctor Oscar Luis Celada said.
It is a further fitness concern for Barca ahead of the Clasico contest with Real Madrid at Camp Nou on April 2, with Ivan Rakitic having pulled out of the Croatia squad with a calf injury.