Matthijs de Ligt will miss the Netherlands' World Cup campaign after undergoing back surgery to address an injury that has kept him out since November.
The Manchester United defender is not expected to return until the early stages of next season.
"Matthijs de Ligt has undergone successful surgery to address a back injury," United said in a statement on Friday.
"Having diligently worked throughout his rehabilitation process, the decision was made that a corrective procedure was the best course of action."
De Ligt had made a positive start to this season, playing every minute of United's first 13 Premier League games until the injury halted his progress.
"Since November I have done everything, pushing myself in every session and exploring every option, to get back to doing what I love, playing football," said the former Juventus and Bayern Munich centre-back.
"I am grateful to everyone who has supported me throughout a difficult period in my career.
"I remain as determined as ever to represent Manchester United and play in front of our incredible supporters as soon as possible."
