Vicente del Bosque is planning to give some of his reserves a run-out in Tuesday's friendly against Chile in Geneva to assess whether they should be part of the squad for next year's World Cup.
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Captain and goalkeeper Iker Casillas, who played in Friday's 2-0 qualification Group I win in Finland, will make way and Victor Valdes and Pepe Reina will both get their chance, Del Bosque told a news conference.
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He did not specify who else might feature, but the likes of defenders Ignacio Monreal and Ignacio Fernandez, midfielder Javi Garcia and forward Roberto Soldado will be hoping for an opportunity to impress.
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"We are going to ring all the changes," Del Bosque said.
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"We will have the chance to allow some players to increase their number of appearances so we can also observe them," he added.
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"We have a very large squad that can respond to any problem. We have people who have given us a great deal and youngsters pressing for a place."
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Spain travelled with 21 players to Switzerland earlier on Monday after Isco and David Villa withdrew from the squad with minor knocks.
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They come into the match having moved to the brink of securing a berth at next year's World Cup finals in Brazil thanks to their comfortable victory in Helsinki.
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Chile coach Jorge Sampaoli, whose side's 3-0 success at home to Venezuela last week means they are third in South American qualifying, said his team would try to dominate possession in the same way they managed in the first half of the last meeting between the two sides.
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Chile were 2-0 ahead at the break in a friendly in September 2011, also played in Switzerland, but a goal from Andres Iniesta shortly after halftime followed by a Cesc Fabregas double secured a 3-2 victory for the world and European champions.
The changes did not change anything about Spain's football. They really need to improve. Chile played very well!