United host Wolfsburg on Wednesday having lost their opening game 2-1 to PSV, with Arsenal and Manchester City also losing to Dinamo Zagreb and Juventus, respectively.
Chelsea were the only Premier League side to win their first group clash, beating Maccabi Tel Aviv 4-0 at Stamford Bridge to go top of Group G.
Van Gaal, who saw his side beat Sunderland 3-0 on Saturday, claims English clubs have the quality to progress in Europe, but face a serious disadvantage compared with clubs from other countries.
"The Premier League is a very difficult league. To beat your opponent every week is not easy, it is always a struggle and a battle," the Dutchman said.
"Then you have to play again mid-week in the Champions League and that is the difference between all the clubs in Europe.
"It is not predictable to say four teams in the Premier League shall overcome this group stage round, no, it is not like that.
"But I have to say that we have the teams to do it and we have the quality to do it."
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Louis van Gaal says Premier League clubs will struggle in the Champions League
Squad rotation is the key to European success, but Van Gaal says even ringing the changes will not guarantee that English sides are fresher than their European counterparts.
"The difficulty is that all these (Premier League) players are in a rat race," he added.
"That takes a lot out of the players, which is why you have to rotate and that is what I am doing now because I have to protect my players.
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Chelsea were the only English team to win their opening Champions League encounter
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Memphis Depay, Juan Mata and Wayne Rooney all scored to beat Sunderland at the weekend
"I say we have to play Sunday-Tuesday, Sunday-Wednesday, so between the matches we cannot recover all of the tiredness.
"Then we have to play against a European squad who is willing to give everything against us.
"They don't have a rat race in their competition and that is the difference."