Strikers Aleksandar Mitrovic and Dwight Gayle will both miss Newcastle's Sky Bet Championship clash at home to Brighton on Saturday - live on Sky Sports 1 HD from 5.15pm - after suffering concussion.
The two men were hurt during the first half of Tuesday night's 2-0 EFL Cup second-round victory over Cheltenham with Mitrovic leaving the pitch before the break and replacement Gayle following him after it.
Manager Rafael Benitez would have loved to have both available for a key game, with Mitrovic having only just returned from a four-game ban, but the club will follow Football Association protocol and not allow them to return until six days after their respective head injuries.
The club's head of sports medicine and science Paul Catterson said: "The treatment and management of concussion in sport has received deserved attention in recent years.
"We have to adhere to the guidelines set out by the FA in line with other competitive sports, which rightly puts the safety and health of players first."
Benitez will have to shuffle his pack once again, although he will at least be able to call upon Ayoze Perez, whose double against Cheltenham opened his account for the season.
Meanwhile, the club has confirmed that midfielder Rolando Aarons will be out for eight weeks after undergoing surgery to repair a fractured metatarsal.
The 20-year-old suffered the break during the Cheltenham game, during which he was substituted after just 24 minutes.
A statement said: "Newcastle United can confirm that Rolando Aarons sustained a fracture of his fifth metatarsal during the Magpies' EFL Cup second round victory over Cheltenham Town on Tuesday.
"The winger will undergo an operation and will be out for eight weeks."
Don't miss Newcastle v Brighton live on Sky Sports 1 HD from 5.15pm on Saturday. Or watch for £6.99 without a contract, on NOW TV.