The defending European and world champions have won all five games so far, including a 3-2 victory in the reverse fixture at Wembley back in Sepmber.
That puts Luis de la Fuente's team on 12 points as group leaders with both sides on course to reach nextt year's quarter finals.
Spain v England team news
The key squad news for Spain in the joint return of Lamine Yamal and Mikel Oyarzabal - who both missed the 2-0 win in Czechia, and should come straight back into De la Fuente's starting XI.
Barcelona star Pedri could also start ahead of clubmate Fermin Lopez.
Thomas Tuchel may opt for changes in defence - with Jarrad Branthwaite and Ben White possibly coming in - but the rest of the team should be unchanged from the 2-1 home win over Croatia.
Spain v England predicted lineups
Spain XI: Simon; Porro, Cubarsi, Pubill, Cucurella; Pedri, Ruiz, Zubmendi; Lamine Yamal, Oyarzabal, Baena.
England XI: Pickford; White, Quansah, Branthwaite, Hall; Rice, Anderson, Bellingham; Rogers, Kane, Gordon.
Spain v England kick off time
Kick off at the Estadio Metropolitano in Madrid is set for 8:45pm local time and 7:45pm in the UK.
Key stat
Spain have come out on top in the last two head-to-heads - including the final of UEFA Euro 2024 - but England won on their last trip to Madrid in 2018.