United's bid to successfully retain the FA Cup for the first time ever meets a major hurdle with a daunting last-eight trip to double-winners elect Chelsea.
The stage is set for a mouthwatering heavyweight contest between the country's two most in-form sides for a place at Wembley.
After winning the first major trophy of the season last month, the Reds have built an impressive run of one defeat in 28 matches in all competitions, that stretches back to October.
Our last meaningful defeat came at the hands of Monday's opponents as the Stamford Bridge side ruined Jose's first return with an emphatic 4-0 defeat.
A repeat of that scoreline looks unlikely, with United a much-improved outfit since then, but Chelsea have only lost once at home this term and are favourites for the domestic double.
Without the demands of European football, Antonio Conte's side have managed to keep their squad fresh, focused and injury-free and the Blues hold an imposing record against us.
We've not beaten them in 11 attempts since 2012 when Robin Van Persie and Chicharito scored in a 3-2 win in west London during SAF's last season.
That's a damning statistic that is sure to affect United psychologically and to make the task even harder, the absence of 26-goal Zlatan Ibrahimovic serves a major blow.
The Reds top scorer and talisman begins a three-match ban after he elbowed Bournemouth's Tyrone Mings during last weekend's 1-1 draw at Old Trafford.
That immediately gives Jose Mourinho a question to answer.
Wayne Rooney was rested for Rostov and could return, Anthony Martial may move into the middle or Marcus Rashford could get his chance up front.
United have, at times, relied on Ibra's strength and firepower this season: his 26 goals in all competitions put him 17 ahead of our second top scorer Juan Mata.
His absence creates problems not just for his goal-scoring but also his aerial ability and influence on the rest of the team.
Zlatan is the inspirational figurehead and leader of the attack and his suspension will make life
easier for Chelsea's back three.
Conte's switch to that system was widely regarded as the turning point of their season, with Tottenham the only team to beat them since.
Mourinho deployed a wing-back system in Russia to match Rostov's shape, and could utilise it again here to deal with the floating threats of Eden Hazard and Pedro.
Whatever system and formation Jose uses, we can be sure that he will have a plan to derail his former club's seemingly unstoppable march to glory.