Louis van Gaal says goalkeeper David de Gea is not ready to start Manchester United's Barclays Premier League game against Tottenham on Saturday.
De Gea has been the subject of interest from Real Madrid all summer.
The Spain international started the final two games of United's pre-season tour of the United States, but is not ready to play in the first game of the season, according to Van Gaal.
"He shall not play," the United boss said.
"I think a human being is more than only a player, and he (De Gea) cannot manage that," Van Gaal added.
Senior figures at United have insisted all summer that the club would only sell De Gea if they received Real Madrid defender Sergio Ramos as part of a swap deal.
"We have problems of course with De Gea," Van Gaal said.
SEE MORE: Peter Schmeichel urges David de Gea to make a decision on his Manchester United future.
Van Gaal has only limited options when it comes to a replacement for their two-time player of the year.
Victor Valdes has been frozen out after Van Gaal claimed the former Barcelona 'keeper told him he would not play for the Under-21 side last season.
Sam Johnstone started the other two games of United's tour but is yet to make a competitive appearance for the club. Last season he spent time on loan at Doncaster and Preston.
The most likely alternative appears to be Sergio Romero, who signed for the club on a free transfer last week.
But when asked if Argentina's number one would start the lunch time kick-off at Old Trafford, Van Gaal said: "You have to wait and see who is starting."
Anders Lindegaard is another option, but the Dane has never played under Van Gaal and is therefore not currently in favour.
When asked what he thought the outcome of the De Gea saga would be, Van Gaal said: "I don't know. That's in process.
"I cannot lead this process – I can only watch and observe and that's what I'm doing, but I'm not participating in it."
The build up to United's season opener has been far from ideal for Van Gaal.
As well as the De Gea situation, the Dutchman has had to stomach the sale of star midfielder Angel di Maria.
United paid £59.7million for the Argentinian last summer, but less than 12 months later he has left for Paris St Germain.
Di Maria claimed at his unveiling in the French capital on Thursday that United wanted him out of the club, but Van Gaal seems to think otherwise.
"For us that's a big loss," Van Gaal said of the former Real Madrid star.
"I want more attackers with speed and creativity. Di Maria is one of those players so we have to look for that kind of player, but they have to have the talent to cope with the English rhythm and that's difficult to find.
"That's why players are not having success in this competition – because of the rhythm of the game and the English culture is another culture as the Latin culture. Maybe that's a reason (he left)."
Although he will not speak publicly on the matter, Van Gaal is expected to sign Barcelona forward Pedro as Di Maria's replacement.
As well as De Gea, Van Gaal confirmed new summer signing Bastian Schweinsteiger is not available for Saturday's curtain-raiser at Old Trafford.
"Schweinsteiger came (to us) at the last moment, out of his holidays," Van Gaal said of the former Bayern Munich midfielder.
"I don't think he's fit enough, so we have to build him to the fitness I think he needs."
Another player who is unlikely to feature is defender Marcos Rojo, who missed the second leg of United's tour because of passport issues.
"Not everybody is ready because players came (back) at a later time," Van Gaal said.
"I like them to come on July 3, but Rojo for example came one week ago."
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