Jose Mourinho's side remained unbeaten over the Christmas and New Year period but slipped further behind leaders Manchester City after a series of draws.
And they now host a Derby team who have rocketed up the Championship table to sit second with promotion a realistic aim for Gary Rowett's side.
MAN UTD INJURIES
Romelu Lukaku can return to the squad after suffering a head injury against Southampton over the festive period but fellow striker Zlatan Ibrahimovic has been ruled out for a month with a knee problem.
Eric Bailly and Michael Carrick are long-term absentees, although the latter is back in training again. Antonio Valencia remains on the sidelines with a hamstring injury but should return to action next week.
Marouane Fellaini had not been expected to return from a knee injury but Jose Mourinho has given the midfielder the thumbs up to play.
MAN UTD SUSPENSIONS
United will be without Ashley Young after the full-back accepted a charge of violent conduct following an elbow on Dusan Tadic during the draw with Southampton, and are in the midst of a three-hame suspension.
MAN UTD POTENTIAL STARTING LINE-UP
Jose Mourinho will likely make a number of changes from his side's win over Everton, though the growing injury list at Old Trafford means his options are limited.
Marcus Rashford will lead the line after missing out at Goodison Park while fellow youngsters Axel Tuanzebe and Scott McTominay will get another chance to stake their claims for further opportunities.
Matteo Darmian and Daley Blind have both been linked with moves away but should start this one while Sergio Romero will deputise for David de Gea.
DERBY COUNTY TEAM NEWS
Midfielder Joe Ledley is a major doubt for the trip to Old Trafford with a back injury while former United youngster Tom Lawrence is hopeful of recovering from a hip injury in time to return to Old Trafford.
Bradley Johnson suffered a knock in Monday's draw against Sheffield United but should be fine to take his place in the matchday squad.
Manager Gary Rowett has suggested he will make changes after the busy festive schedule and has not ruled out changing his whole starting XI.
TV COVERAGE & KICK-OFF TIME
The match at Old Trafford kicks off at 20:00 GMT (15:00 ET) on Friday but is not being shown live in the UK.
In the US, you can watch the FA Cup live and on-demand with fuboTV (7-day free trial).
BEST OPTA MATCH FACTS
This will be the 10th time these two sides have been drawn together in the FA Cup, meeting as recently as January 2016 – with Man Utd winning 3-1 at the iPro Stadium in the fourth round.
The Red Devils have won each of the last seven FA Cup games against Derby, including two semi-final wins in 1948 and 1976.
Manchester United haven’t lost to two different sides from outside the top-flight in a single season since 1983/84, when they lost to Oxford United and Bournemouth; the Red Devils lost 2-1 to Bristol City in the League Cup quarter-final this season.
Man Utd have lost just one of their last 35 FA Cup games against lower league opponents at Old Trafford (W28 D6) – losing 0-1 to Leeds United back in January 2010.
The Rams have only progressed past an opponent from a higher division in one of their last 15 FA Cup ties – beating West Brom at the Hawthorns at this stage last season.