The rival nations last met in the 2018 World Cup and put on a memorable show as Cristiano Ronaldo’s hat-trick completed Portugal’s comeback to draw 3-3, capped by Ronaldo’s brilliant free-kick.
The game will act as preparation ahead of the Nations League fixtures later in this international break.
Portugal are currently top of their Nations League group 3 ahead of France on goal difference, and face a trip to Paris on Sunday before meeting Sweden in Lisbon next week.
Spain are top of group 4 and meet Switzerland in Madrid on Saturday before taking on Ukraine in Kiev.
When does the game start?
Portugal vs Spain kicks off today, Wednesday 7 October, at 7.45pm BST.
How to watch on TV and online
The match will broadcast live on Sky Sports Football in the UK. Sky Sports subscribers can watch it online via the Sky Sports website, and via the Sky Go app.
It’s a hard one to call as both sides are likely to rotate heavily. Spain traditionally have greater squad depth but Portugal are a strong proposition these days, and we expect them to put on a good show. Portugal 2-1 Spain.