Spain and Croatia both began their League A Group 3 campaigns with victories, with Spain beating England 3-2 away and Croatia defeating the Czech Republic 2-1.
However, with four Nations League matches being played in a short period, De la Fuente is expected to rotate his squad when Croatia visit Seville.
"Playing four matches at this level within ten days is extremely exhausting," De la Fuente said.
"There are players we want to give a break. We need to refresh the team a little. Not only for this reason, but also because the reserve players deserve it.
"This does not worry me at all. The players who take part will be the most prepared."
Lopez is one of the players pushing for an opportunity after returning to the Spain squad following an impressive start to the season with Barcelona.
The 23-year-old has scored four goals and provided two assists in his first four La Liga appearances, earning a recall after missing the 2026 World Cup because of a foot fracture.
"It was tough because I think I deserved to be there," Lopez told Mundo Deportivo after being selected for the current Spain squad.
De la Fuente has now given Lopez another major boost by highlighting the midfielder's ability to influence games in several different ways.
"He's in fantastic form, just like Dani Olmo," the Spain coach said.
"He gives us energy, vitality, intensity, a lot of talent, class and finishing ability. He's a world-class player and fits perfectly with our style of play."
Lopez is also set for a special night in Seville, with members of his family expected to attend the match.
The Barcelona midfielder will be hoping De la Fuente's praise translates into significant minutes when Spain take on Croatia at the Ramon Sanchez-Pizjuan Stadium.
Anthony Gordon believes his move from Newcastle to Barcelona has changed perceptions of him, with the England international feeling his technical and tactical qualities are finally receiving greater recognition.
Martin Odegaard has missed Norway's training session on Tuesday after picking up an ankle problem during the 2-1 Nations League defeat by Portugal.
Bayern Munich have received a positive fitness update with Konrad Laimer returning to the Austria squad after recovering from an adductor problem.
Real Madrid president Florentino Perez has been summoned to appear in a Madrid court after Barcelona took legal action over comments he made about the club and the refereeing scandal.
