Luis Enrique's side won 2-1 at Wembley in their opening game of Uefa's new competition, as the Three Lions will be out to secure their first points in Group A.
SunSport's top tips will appear on this page ahead of kick-off.
When does Spain vs England kick-off?
This UEFA Nations League fixture takes place on Monday October 15.
It will kick-off at 7:45 pm UK time.
The game is being played at Estadio Benito Villamarin in Seville.
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What TV channel is Spain vs England on and can I live stream it?
The game will be shown live on Sky Sports Main Event.
Sky subscribers will be able to get this online and on the Sky Sports Mobile app.
Or if you're not a Sky subscriber, you can watch all the action live with a NOW TV Sports Pass from £7.99.
What is the team news for Spain vs England?
Jadon Sancho made an impressive debut during the drab 0-0 draw in Croatia on Friday – and will be hoping for more minutes from the bench against Spain.
Gareth Southgate has no fresh concerns, with Ben Chilwell expected to start once again after injuries to Danny Rose and Luke Shaw.
Spain will be at full-strength as they look to make it two wins in two against England with Sergio Ramos expected to pick up his 160th La Roja cap to take him within seven of equalling Iker Casillas' record.
The Spanish captain will be keeping Harry Kane in check, after stating in his press conference that the Tottenham striker would be a success in La Liga.
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