MADRID — With Lionel Messi rested, Argentina was crushed 6-1 by Spain on Tuesday, with Real Madrid midfielder Francisco "Isco" Alarcon scoring his first career hat trick.

Messi watched from the stands at the Wanda Metropolitano Stadium in Madrid as Spain dealt Argentina a humbling loss in the last match before their coaches pick their squads for this summer's World Cup.

Spain remained undefeated in 18 matches under Julen Lopetegui and strengthened its credentials as a favourite for the title in Russia.

Lopetegui said he congratulated his players, but reminded them that this was only a preparation match.

"The reality is that nothing has started yet. We will begin the World Cup with zero points," Lopetegui said.

Jorge Sampaoli, however, will face more doubts about Argentina's chances to finally win a World Cup title with Messi after seeing his supporting cast so thoroughly outclassed.

Diego Costa, Thiago Alcantara and half-time substitute Iago Aspas also scored for Spain. Nicolas Otamendi scored Argentina's goal that made it 2-1 at halftime.

A minor leg problem kept Messi from playing in Argentina's 2-0 win over Italy in Manchester, England, on Friday.

Sampaoli had said on Monday that his star player was better and that he expected him to play against Spain, but he left him out of his squad come match time.

Sampaoli said after the match that if the game had not been a friendly Messi would have played.

"Leo had been training well with us this week but he was still bothered by his leg, and after the last practice session he felt that fatigue," Sampaoli said. "Obviously, we noticed his absence."

The match was intense and ended in a brief scuffle after hard foul by Argentina's Cristian Pavon to cut down Jorge "Koke" Resurreccion.

Gonzalo Higuain was in Argentina's squad for the first time since June, but did little to improve his chances of being on Sampaoli's World Cup list when he tapped a cross by Maximiliano Meza wide from close range eight minutes into the match.

Costa struck first for Spain after Andres Iniesta recovered the ball near Argentina's area and Marco Asensio slipped a ball for the Atletico Madrid striker to bundle past goalkeeper Sergio Romero.

Both Costa and Romero briefly writhed on the turf following their collision, and Romero needed to be substituted 10 minutes later. He was replaced by Willy Caballero.

Asensio again undid the defence when he squared a pass from the right flank to meet Isco's run in from the left side. Isco used one touch of his right boot to slot the ball home.

Otamendi pulled one back when he headed a corner kick through the arms of goalie David De Gea in the 37th.

The second half, however, was all Spain.

Isco fired in a pass by Aspas in the 52nd after the striker deftly controlled a long pass by Iniesta to break behind the defence.

Thiago drilled in Spain's fourth in the 55th when Isco crossed for Aspas, whose bobbled control fell right into the path of the Bayern Munich midfielder.

Argentina's defence was caught off-guard by De Gea's long ball right down the pitch that Aspas ran onto and stroked past the on-rushing Caballero in the 73rd.

Isco then intercepted a pass by Otamendi and combined with Aspas to get his third goal in the 75th.

Marco Alonso and Dani Parejo debuted for Spain late.