De la Fuente led his side to the 2026 FIFA World Cup title in June, on the back of winning the UEFA European Championship in 2024, and he's forced into some rotations.
Barcelona pair Joan Garcia and Gavi both miss out due to injury and fitness issues with Josep Martínez and Fermin Lopez coming in after the latter missed the World Cup with a foot problem.
Marcos Llorente's international retirement means a recall for Real Madrid's Dean Huijsen after a strong start to the campaign at Real Madrid.
Borja Iglesias has also been omitted by De la Fuente, with a shock first call up for Espanyol's Roberto Fernandez, who has scored six goals so far this season.
Spain take on England at Wembley Stadium on September 26th, followed by home games against Croatia (September 29th) and Czechia (October 3rd) and away clash against Croatia (October 6th) to complete the expanded international break.
Spain squad in full:
Goalkeepers : Unai Simón, David Raya, Josep Martínez.
Defenders: Pedro Porro, Eric Garcia, Pau Cubarsí, Aymeric Laporte, Marc Pubill, Dean Huijsen, Marc Cucurella, Alejandro Grimaldo.
Midfielders: Rodri, Martin Zubimendi, Pedri, Fabián Ruiz, Mikel Merino, Dani Olmo, Alex Baena, Fermín Lopez.
Forwards: Nico Williams, Yeremy Pino, Mikel Oyarzabal, Ferran Torres, Roberto Fernández, Lamine, Yamal and Víctor Muñoz.