Rafa Benitez fears he will be without Florian Lejeune and Paul Dummett for several weeks.
Dummett pulled up with a hamstring problem early in the game, while Lejeune hobbled off after Harry Kane caught him late in the club's Premier League season-opener.
Newcastle – who also had stand-in captain Jonjo Shelvey sent off for stamping on Dele Alli – lost 2-0 at St James's Park.
Asked about the injuries suffered by Dummett and Lejeune, United manager Benitez said: “It’s too early.
"The main thing is we lost two players and we had to adapt everything. To lose another (Shelvey) wasn’t nice. Dummett is a couple of weeks, for sure."
Benitez was unhappy with Kane's challenge on summer signing Lejeune, who was making his Premier League debut.
“I would also like to say that the tackle from behind from Harry Kane was worse (than Shelvey's stamp)," said Benitez.
"The rules are the rules, and we paid for that."