Without star man Lionel Messi due to injury, Argentina slipped to a 6-1 thrashing against Spain at the Wanda Metropolitano on Tuesday.
Diego Costa put Spain in front, Marco Asensio then added his second assist of the game by setting up Isco, although Nicolas Otamendi headed one back for Argentina before the break.
That proved a mere consolation for the visitors, though, with Isco on target again shortly after the restart to put Spain in total control.
The Real Madrid playmaker continued to build on an eye-catching individual performance by helping to tee up Thiago Alcantara for Spain’s fine fourth, Lopetegui’s side sending a warning shot ahead of the World Cup with a fifth via substitute Iago Aspas, who set up Isco to claim the match ball soon after.
Watch: Spain 6-1 Argentina