Manager Louis van Gaal said Manchester United have only one senior centre-back available for Saturday's Premier League game against West Ham.
Marcos Rojo is fit, but Chris Smalling (leg), Phil Jones (hamstring) and Jonny Evans (ankle) are injured and Tyler Blackett is suspended.
Van Gaal said: "All three of my right-sided centre-halves are out, so I'll have to go to the youth system."
Potential candidates to play include Tom Thorpe, 21, and Paddy McNair, 19.
Neither under-21 captain Thorpe nor McNair, who joined United as a midfielder three years ago, have played for the first team.
Smalling limped out of training on Wednesday and, with Luke Shaw expected to make his debut at left-back following his £28m summer arrival from Southampton, Rojo is likely to move to centre-half against the Hammers.
"I won't take risks with players - they have to be fit," said Van Gaal, who is without nine players in total through injury.
Midfielders Daley Blind or Darren Fletcher could be employed as centre-backs by United, who are 12th in the table with only one win from their first five games.
But Van Gaal denied it would be a risk to select the younger players.
"They have hunger to play the game and the Manchester United youth education system has a certain level that can provide that," said the Dutchman.
Van Gaal admitted there was a "big difference" between youth football and Premier League, but added: "In one game you can show yourself."
Asked if there was a sense of panic after United let slip a 3-1 lead in losing 5-3 at Leicester City last weekend, he said: "No. It's happened - it's about overcoming things.
"It's not a regular occurrence. When you see our figures in the Premier League - with the exception of the Leicester match - then we are defending well.
"I don't think my players are robots - they are human beings and human beings make errors."