When: Friday, June 4, 18:30 BST
How to watch: Sky Sports
With the European Championships just around the corner, time is running out for managers to complete their pre-tournament preparations.
Portugal, who are the defending European champions, come into this game with good form. Fernando Santos' side have lost just one of their last 13 international outings and that defeat came against world champions France.
Spain, on the other hand, are also in decent form having lost one of their last 22 games. However, with Luis Enrique's men conceding six goals in seven games, there's certainly room for improvement.
Last Three Matches
Portugal 0-0 Spain (Friendly - October 7, 2020)
There's little to say about the last head-to-head fixture between Portugal and Spain.
The Spaniards enjoyed majority of possession, produced more shots on goal and created more attacks but in the end, they failed to find a breakthrough.
Portugal 3-3 Spain (World Cup - June 15, 2018)
There was certainly nothing boring about this one.
Cristiano Ronaldo opened the scoring with a well converted penalty when these two sides clashed at the 2018 World Cup.
Diego Costa levelled things up in the 24th minute however, Portugal soon retook their lead with a second goal from CR7.
The second half belonged to Spain as a second goal from Costa and a first for Nacho saw the former World Champions move 3-2 ahead.
Nevertheless, it was Ronaldo who had the final say as he bagged an equaliser in the 88th minute.
Portugal 0-0 (2-4p) Spain (Euro 2012 - June 27, 2012)
The last Iberian Derby to take place at a European Championship took place in 2012 when Portugal and Spain clashed in the semi-finals.
This was a tense affair which ended 0-0 after 120 minutes of football.
As the game entered penalties, Spain showed outstanding composure to take the win and bag a spot in the final.
Last ten head-to-heads
Spain wins: 3
Spain goals: 11
Portugal goals: 11
Real Madrid players blanked by Spain
This is something that has never happened in the history of the Spanish national side. However, they came close in 1950 when only one Real Madrid star - Luis Molowny - made the selection.
Ultimately, Enrique's decision will be judged by results at the upcoming Euros. Success in the tournament would certainly justify his strategy.
Portugal stronger but facing difficult challenge
Some would argue that the Portugal squad of today is stronger than the one which won the 2016 European Championship.
With the likes of Diogo Jota, Andre Silva and Bruno Fernandes joining the squad, it's no surprise to see Portugal as fourth favourites to retain their title.
One reason why they aren't ranked higher is due to the difficult task facing them in the group stage.
Diogo Jota is in great form for Portugal. The Liverpool man has scored three first-half goals in his last two international outings.
The forward is currently priced at 8/1 (Betway) to score first against the Spaniards.