Defender Ciaran Clark has picked up a thigh strain on international duty with Republic of Ireland and is a now a doubt for the weekend.
Clark has been pulled out of tonight's Nations League game against Wales and will return to Tyneside to be assessed by the club's medical staff.
A statement said: "The club has been informed by the Football Association of Ireland that Ciaran Clark will not be fit for his country's UEFA Nations League game against Wales on Tuesday evening.
"The Newcastle defender suffered a thigh injury during training ahead of the match.
"He will be assessed further on his return to Newcastle later this week."
Clark was on the bench for Newcastle's last Premier League game as the Magpies lost 3-2 at Old Trafford against Manchester United.
He is behind the first-choice central defensive pairing of skipper Jamaal Lascelles and summer signing Federico Fernandez.
Newcastle boss Rafa Benitez, meanwhile, is hoping defender Paul Dummett is fit for the visit of Brighton to St James's Park this week.
The left-back didn't join up with Wales during the international fortnight after suffering a hamstring strain, but has returned to training this week.
Dummett has missed Newcastle's last two league games.