This is a match made even more interesting by La Roja's decision to part company with manager Julen Lopetegui just two days before this game after he agreed to become the new Real Madrid boss.
Spain are favourites to win the game priced at 21/20 (2.05) with Coral, who are 3/1 (4.0) on the European champions springing something of a surprise, while the draw is available at 21/10 (3.10) with the same firm.
The Iberian neighbours are expected to progress from Group B to the knockout stages and this clash will go a long way to deciding which of them has the best chance of doing so as winners.
While the match isn’t expected to be a particularly high scoring affair, the likelihood of tempers flaring looks much more assured and that could be a profitable approach for punters to take on Friday evening.
Coral have another huge new customer offer to add to the excitement going 25/1 (26.0) on any player being shown a card during the match. £1 bet. Winnings paid in free bets. Terms and conditions apply.
If the previous meeting between the pair at the European Championships six years ago is anything to go by, this match promises fireworks galore and a busy referee.
On that occasion a total of nine players were booked and given that the likes of Pepe, Sergio Ramos and Sergio Busquets remain in their respective national team set-ups, a bad blooded affair can't be overlooked here.
Even Portugal's 4-0 friendly win in 2010 saw three bookings so meetings between the European neighbours are rarely quiet on the disciplinary front.
With that kind of history, plus another highly-charged encounter in prospect here, the chance to get a quote of 25/1 (26.0) about any player being shown a card is not to be missed.