La Roja's penalty shootout defeat to hosts Russia at this summer's World Cup was a shock, but in the grand scheme of things it was perhaps predictable given the disrupted buildup to the tournament.
Here, Sports Mole looks at how Spain could line up against the World Cup semi-finalists.
Spain have been hit by a number of retirements in the wake of the World Cup, with Gerard Pique, Andres Iniesta and David Silva all calling time on their international careers, but 156-time capped Sergio Ramos remains and will move to within 10 appearances of all-time record-holder Iker Casillas at Wembley.
Diego Costa's withdrawal for personal reasons should see Chelsea striker Alvaro Morata lead the line, with Real Madrid duo Isco and Marco Asensio in support if Enrique sticks with the 4-3-3 formation he favoured at Barcelona.
Dani Ceballos and Pau Lopez are other potential debutants for La Roja, although neither is expected to start against England with David de Gea continuing in goal and Saul Niguez, Sergio Busquets and Thiago Alcantara making up the midfield.