The Netherlands striker has not trained sufficiently since returning from the World Cup to be considered as the Red Devils chase a second successive opening day win over the Swans
The striker returned to pre-season training late after reaching the World Cup semi-finals, under Van Gaal, with the Netherlands.
And, asked whether Van Persie might be fit enough to play on Saturday, Van Gaal said: "No chance. He has to train."
The comments echo the former Bayern Munich and Barcelona coach's statement from earlier this month, when he predicted Van Persie would not be ready.
"Robin wants to play every game, I know that, but so do the other 30 players in the squad," he said at the time. "But players have to train and Robin needs a full training regime behind him before he can play again."
Big-money signing Luke Shaw will also miss out on Saturday after picking up a hamstring injury, but Van Gaal is confident of filling the gap left by the teenager.
"We played in the USA [pre-season tour] with Reece James and Ashley Young in that position [left wing-back]," he reminded reporters. "I'm not worried."
Sam Johnstone, Antonio Valencia, Jonny Evans and Danny Welbeck all join Shaw in being unavailable for the Premier League curtain-raiser through injury.