Jose Mourinho had stated at a pre-match press conference on Friday that the £89 million midfielder would start Saturday's fifth-round meeting with the Terriers.
The Portuguese had previously been forced to fend off speculation regarding a possible summer transfer for the France international and talk of a rift between player and coach at Old Trafford.
It was hoped that Pogba and Mourinho could display a united front at the John Smith’s Stadium, but an untimely sickness bug has sidelined the 24-year-old.
A statement on United’s official website read: “Manchester United midfielder Paul Pogba will miss the Emirates FA Cup tie at Huddersfield Town due to illness and, as a result, Academy prospect Ethan Hamilton has taken his place in the squad.
“The young and industrious Scottish midfielder has impressed during his seven UEFA Youth League appearances this campaign, scoring one goal for Nicky Butt’s exciting team. Aged 19, he is also a regular in the club’s Under-23s team and featured on Friday night against Chelsea at Leigh Sports Village.
“This is Hamilton’s first inclusion in a first-team squad and we can confirm the youngster will wear the no.48 shirt at the John Smith’s Stadium, where the FA Cup fifth-round tie is scheduled.
“Ethan joined United when turning 16 after playing for Hutchison Vale, a local boys club the Reds have dealt with before when Darren Fletcher represented the Edinburgh-based youth team.”
Losing Pogba deals a substantial blow to United’s plans, but Hamilton will be relishing an opportunity to join the senior fold.
United’s Under-18s manager Kieran McKenna said of the youngster: “He is a fantastic character around the group and another one with a great training mentality every day. He's a hard worker who wants to get better and develop himself.
“He's a really solid player for the group as well as being a good talent. With his attitude, it could certainly carry him very far in his career.”
Pogba, meanwhile, took to Twitter to register his disappointment at missing out on the fixture.
Gutted I won’t be at Huddersfield but I need to get better. Come on United @ManUtd— Paul Pogba (@paulpogba) 17 de febrero de 2018
"Gutted I won’t be at Huddersfield but I need to get better. Come on United," the midfielder wrote after his absence was confirmed.
The Red Devils also have crunch clashes against Chelsea and Liverpool to come over the coming weeks, so getting key men fit and firing will be a top priority for Mourinho and his coaching team.