"To play so many kids at the same time, honestly, I don't think is good. You want them to be surrounded by players who support them," said the Portuguese.
United are guaranteed sixth place, while Palace are safe from relegation.
Sam Allardyce's side are 13th going into the match at Old Trafford (15:00 BST kick-off), but a victory and other results going their way could see them finish as high as 11th.
Mourinho's side face Ajax in the Europa League final in Stockholm on Wednesday knowing victory will earn them a place in the group stages of next season's Champions League.
Who are the youngsters?
Goalkeepers: Kieran O'Hara (21), Joel Castro Pereira (20).
Defender: Demetri Mitchell (20).
Midfielders: Zachary Dearnley (19), Angel Gomes (16), Josh Harrop (21), Scott McTominay (20), Matthew Willock (20).
In addition, striker Marcus Rashford, who has 11 goals this season, defender Timothy Fosu-Mensah, who has played 10 times this season, and Axel Tuanzebe, who has played four times, should be in the United squad on Sunday. All three are 19.
'I know the kids'
United have already won the EFL Cup this season, and Mourinho's team selection has Wednesday's Europa League final in mind.
Mourinho said Paul Pogba - the world's most expensive player - will play on Sunday having missed the past two games after the death of his father, while fellow midfielder Marouane Fellaini will have a scan on a hamstring injury.
Meanwhile, captain Wayne Rooney - who has been linked with a summer transfer - may have missed the chance of an Old Trafford farewell, as Mourinho said the England international would "probably not" be involved.
"It's a great experience for the kids but they are not ready. Maybe one at a time but not all together," added the former Chelsea manager.
"I spoke with [Under-23 coach] Nicky Butt and his opinion is important. When they played at Old Trafford, I have been there. They trained with me many times. I know the kids.
"We bring the ones who are more adapted to our team at the moment. Our biggest problem is the number of matches. It is unbelievable."
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