Spain face their first opponents since their shock World Cup last-16 exit to hosts Russia and it comes against semi-finalists England.
New manager Luis Enrique has picked a mixture of fresh faces and Spanish veterans and here Press Association Sport looks at the key men in La Roja’s squad.
David De Gea
Having only kept one clean sheet in four Premier League games for Manchester United, De Gea shot-stopping abilities will be key for Spain, who are likely to be tested by a confident England side. The 27-year-old has become one of the world’s best over recent years and will want to show his class at Wembley on Saturday.
Following Jordi Alba’s omission from the squad, recalled Chelsea left-back Alonso becomes a key component down the flank. With wingers Isco and Marco Asensio likely to drift infield, it will be down to Alonso to provide a threat from wide areas.
Captain through a tough World Cup campaign, Ramos has an important role of bringing the squad back to full confidence again. The Real Madrid defender will need to bring his impressive club form to the national side.
Having spent many years in the squad while Sergio Busquets dictates the tempo, the Bayern Munich midfielder is now a vital cog in Spain’s well-oiled passing machine. His vision and accurate passing will be key for Spain as they look to unlock England’s defence.
Isco will be the man tasked with the creative responsibilities. He achieved a 91.4 per cent passing accuracy at the World Cup in Russia, higher than David Silva’s, and completed nine key passes. The Madrid star will be the one Spain turn to when they are in need of a creative spark.