"After this, an important generation is going to leave and many players are going to change".
Of Messi's potential absence, Saul Niguez said: "Argentina has a great team".
"Passing by the World Cup trophy was disgusting".
The Barcelona star was ruled out of his country's 2-0 friendly win over Italy in Manchester on Friday due to a hamstring problem.
Spain's Isco (left) and goalkeeper Pepe Reina (right) attend a training session of the Spanish national team at Wanda Metropolitano stadium in Madrid, Spain.
Argentina count on players such as Atletico's Angel Correa, while Ever Banega is at Sevilla and Gonzalo Higuain spent several seasons with Real Madrid.
"There isn't another, you have to think about this World Cup as the last and try to take advantage of the chance".
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Nevertheless, the occasionally feisty nature of their Clasico showdowns does not give Sampaoli any cause for concern over Messi's fitness. "Leo is unreachable", Sampaoli said.
"But here, he did a fitness test yesterday (Sunday), he did another one today and he's fine".
Spain drew 1-1 with World Cup holders Germany in Dusseldorf on Friday, and the 2010 winners are now being considered among the pre-tournament favourites by some.
"It's not correct to say that Paulo is out of the World Cup", the Albiceleste boss said in his pre-Spain Press conference.
"When we're preparing for a game we're not thinking about what's in front of us", Lopetegui said.
"It's tougher for us to play in that area".
"Leo has to play like he does for his club, to put him into another structure is madness", added Sampaoli, who had suggested that football owes Messi a World Cup after the superstar scored a hat-trick to help them clinch the must-win qualifier against Ecuador last October.