Match Odds: Draw
Spain have lost just once on home soil since October 2018 and head into this match on the back of four successive victories, with their most recent being an emphatic 5-0 victory against Iceland in March.
But a draw is perhaps the most likely result given the history of this fixture.
The last four meetings between the two sides have ended all square, three of which have been 0-0.
The other game in that sequence, which took place at the 2018 World Cup, finished 3-3, with Portugal captain Cristiano Ronaldo scoring a hat-trick.
First Goalscorer: Cristiano Ronaldo
Ronaldo’s return to Manchester United has not gone to plan but he remains one of the most prolific players on the planet.
The 37-year-old became the leading scorer in the history of men’s international football earlier this year and ended his first season back at Old Trafford with 24 goals in all competitions.
Ronaldo is favourite to be first goalscorer here, but the iconic No. 7 is not going to be the only world-class forward on display.
His United team-mate, Bruno Fernandes, is likely to start after scoring twice in Portugal’s World Cup play-off final against Macedonia in March.
So is Diogo Jota, who appeared as a substitute in Liverpool’s Champions League final defeat to Real Madrid on Saturday.
Spain boss Luis Enrique doesn’t have the same firepower to call upon as his opposite number Fernando Santos.
Raul de Tomas, of Espanyol, and Alvaro Morata, who spent this season on loan at Juventus from Atletico Madrid, are their most likely goalscorers, according to the latest odds.