Isco scored a hat-trick as Spain hammered an Argentina side without Lionel Messi 6-1 in a friendly, while Brazil defeated Germany 1-0 in their first meeting since the 2014 World Cup.
Gareth Southgate's England were denied victory over Italy at Wembley after the visitors were awarded a disputed late penalty in a 1-1 draw following consulation with the video assistant referee.
Spain underlined their status as chief contenders at this year's World Cup in Russia as they extended their unbeaten run under Julen Lopetegui to 18 matches in sensational fashion in Madrid.
Diego Costa bravely forced home Spain's opening goal on 12 minutes and Isco doubled the lead before Nicolas Otamendi halved the deficit prior to half-time.
The absence of Messi, left out of the squad by Jorge Sampaoli despite the coach insisting on Monday that his star striker was fit, was telling as Spain dominated the South Americans in the second half.
Isco bagged his second on 52 minutes and Thiago Alcantara swiftly added another for the hosts before substitute Iago Aspas struck after latching onto a long downfield pass from David de Gea.
The mauling was complete when Isco sealed his treble on 74 minutes, capping a starring performance while leaving Sampaoli with questions to answer with the World Cup less than three months away.
"We're very happy to beat the finalists from the last World Cup, a team with a fantastic history," Lopetegui said.
"But that doesn't change anything for this World Cup, we will have to start with zero points (in the group stage)."
- Mbappe, Lukaku shine -
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"I'm glad it's not the World Cup just yet," said Southgate. "I think the ruling is 'clear and obvious' and it's not. It's one you can debate all day."
"He was also playing a 'comeback' match, because it's been a while since he played a full game, it'll do him a lot of good."
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