Rafa Benitez will hand Florian Lejeune his comeback against Blackburn Rovers.
Benitez – who has lost Mohamed Diame to injury and Yoshinori Muto to the Asian Cup after Wednesday night's 2-0 home defeat to Manchester United – will "change some players" for Saturday's third-round tie at St James's Park.
Lejeune ruptured his anterior cruciate ligament in pre-season.
The 27-year-old will get some minutes against the Championship side, having returned to fitness in just five months after pioneering surgery.
"He's fine," said United manager Benitez, who is expected to hand 21-year-old midfielder Sean Longstaff a start against Blackburn.
"He was playing for the Under-23s for 45 minutes, so we didn't want to expose him in this type of game knowing the pace of the game for a player who has been away for so long.
"It's very difficult, but he's ready, he's available, so hopefully we can give him some minutes in the next games."
Asked how he would approach the tie, Benitez said: "Obviously, we will change some players, but we will have the same idea – to put a team on the pitch that will be good enough to go through.
"The priority is the next game. After, we will see where we are."
Meanwhile, midfielder Diame limped off against Man United, while forward Muto has linked up with his Japan team-mates ahead of the Asian Cup, which kicks off this month.
"Diame has had this problem in the past," said Benitez. "Hopefully, in a couple of days he will be fine. He was trying to continue. Normally, after a few days he is fine.
"We will see how they are. We have enough players, and if not, we have to keep an eye on the young lads."