The Dutch striker was replaced by Klaas Jan Huntelaar with 15 minutes left of the weekend's clash against Mexico, despite the fact that his side trailed 1-0 at the time.
However, rather than having concerns over his fitness, Van Gaal has insisted that Van Persie, who will be managed by the 62-year-old at Manchester United next season, was substituted for "tactical" reasons.
"The substitution of Van Persie was tactical. Let's not forget that before he joined the squad he was recovering from an injury. It's difficult for him to keep up 90 minutes especially in these [hot] conditions," he told reporters.
"Anyway, this trainer wants to win. So he makes the changes and the substitutions he needs. It's simple. Nothing else matters."