Newcastle boss Eddie Howe said his side are “dangerously close” to not being able to field a team for their Premier League game at Everton on 30 December.
Forwards Callum Wilson and Allan Saint-Maximin both then suffered injures during the game at St James’ Park.
Howe fears Wilson could be facing “months” on the sidelines.
Newcastle are 19th in the table, two points behind 17th-placed Watford.
“Callum’s injury looks severe, weeks maybe months,” Howe told BBC Radio 5 Live. “I feared for him when he went down with nobody around him. A pull, not a knock.”
The Newcastle boss could only name eight substitutes against Manchester United, including two goalkeepers and two teenagers who had not started a Premier League match.
“The lads gave everything but we are thin on the ground in terms of bodies,” he told Sky Sports.
“These are difficult moments for us. I believe it’s 13 plus a goalkeeper [to have enough players for a game]. We’re going to be dangerously close to that number.”
Wilson, 29, went off in first-half injury-time holding his calf and Saint-Maximin, who scored after seven minutes and missed a chance in the second half, pulled up with a hamstring problem after Edinson Cavani had scored an equaliser.
“Allan, I don’t think is as serious [as Wilson] but serious enough to bring him off.”
Newcastle, who have now played three games more than Watford and four more than 18th-placed Burnley, were already without defenders Jamal Lewis, Federico Fernandez and Paul Dummett, while midfielder Isaac Hayden was suspended.
However, goalkeeper Karl Darlow, defender Ciaran Clark and midfielders Matt Ritchie and Joe Willock were also all missing from the squad for the match against Manchester United.
Newcastle have scored 19 goals in 19 Premier League games, with top scorer Wilson getting six of them, while 24-year-old Saint-Maximin has four league goals.
Scotland winger Pat Nevin, part of BBC Radio 5 Live’s commentary team, felt Newcastle would greatly miss those players.
“We don’t know how bad the injuries are,” said Nevin. “Callum Wilson was having a great game before he pulled up before half-time.
“He’s not just a goalscorer, he holds the ball up so well. But if Allan Saint-Maximin is out for anything more than a week or two then it would be a disaster. They need their best two players so the cost to them is absolutely immense.
“Eddie Howe needs time to get these players back and also to bring in other players.”
Fifteen top-flight matches have been called off this month, including Arsenal v Wolves and Leeds v Aston Villa, which had both been scheduled to take place on 28 December.