The likes of Pedri, Jordi Alba, Alvaro Morata, Marcos Llorente and Thiago Alcantara are all injured and unavailable for Luis Enrique this month, while Gerard Moreno and Dani Olmo are also out of contention.
Koke and Sergio Busquets are both good to go in midfield, while Pedri's spot will most likely be filled by Real Sociedad's Mikel Merino, unless Enrique decides to take a punt on Barcelona teenager Gavi.
With no Morata to spearhead the attack, Ferran Torres could be deployed furthest forward as he has done for Manchester City, with Pablo Sarabia and Mikel Oyarzabal expected to feature out wide ahead of Llorente's replacement Bryan Gil.
Spain possible starting lineup: Simon; Azpilicueta, Torres, Laporte, Reguilon; Koke, Busquets, Merino; Sarabia, Torres, Oyarzabal
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