Manchester United visit Huddersfield Town's John Smith's Stadium for the first time in Friday night's FA Youth Cup tie.
Paul McGuinness' side have successfully navigated matches on the road in rounds three and four and the reward for the victors will be another away clash against either Manchester City or Fulham.
James Wilson was not risked in the Under-21s' win against West Ham on Monday due to illness while Andreas Pereira is also expected to be available despite being substituted late on at Old Trafford. Ashley Fletcher has been sidelined since undergoing knee surgery.
The Reds' 4-2 defeat to Blackburn Rovers last weekend was a fourth successive reverse in the Barclays Under-18 Premier League but the team still sit in fourth place, which would be enough to clinch qualification for the semi-finals of the competition.
The FA Youth Cup always takes priority due to the club's special relationship with the tournament, having won it more often than any other side, and a sizeable crowd is anticipated for the Valentine's Day encounter.
"Huddersfield are a well organised team," explained McGuinness to MUTV. "They have got Frankie Bunn and Mark Lillis in charge, two very experienced guys, who have them well drilled and organised. They are doing well in their league and deserved to go through against West Brom [in the last round].
"It will be a tough game, no doubt about it, and it's away from home again, which is a good challenge. None of these games is easy and it's probably the biggest game of their lives for all these players."
McGuinness feels it is imperative for the Under-18s to go on a run in the competition in order to obtain valuable experience to aid them in their careers.