The Barcelona pair are withdrawn from La Roja's starting XI after a 5-1 humiliation by Netherlands, with Pedro and Javi Martinez to step into breach against ChileSpain boss Vicente del Bosque has made two changes his starting XI to face Chile, dropping Xavi and Gerard Pique to the bench.
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The highest-profile players to drop out of the panel for the clash are the Barcelona duo, with club-mate Pedro and Bayern Munich's Javi Martinez brought into the fold.
Xavi and Pique have accumulated nearly 200 international appearances between them and have been among the bedrock of a team who have won all of the last three major international competitions that they have entered.
Martinez is more typically a holding midfielder than a centre-back, where he has been used sparingly by Pep Guardiola at club level, but has been preferred to both Pique and Raul Albiol in the defence for this vital game.
No other changes have been made by Del Bosque, who has otherwise kept faith with a side so intensely criticised after their opening match.
Spain starting XI: Casillas; Azpilicueta, Ramos, Martinez, Alba; Busquets, Alonso; Pedro, Silva, Iniesta; Costa