When Lisandro Martinez was stretchered off the pitch at Old Trafford on Thursday night, a frustrating night became disappointing.
That disappointment on the terraces suddenly became despair just minutes later when Sevilla scored again to make the game 2-2. United had thrown away a two-goal lead and they'd lost their first-choice centre-backs to injury.
When it rains, it tends to pour in Manchester. Erik ten Hag could not give an update on either Raphael Varane or Martinez during his press conference on Friday afternoon and it seems like both players are facing a spell on the sidelines.
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The early suspicion is Varane should be back sooner rather than later, but that Martinez could be out for a longer period with a fractured metatarsal, which can take up to nine weeks to recover from, especially if surgery is required.
The result against Sevilla was disastrous, but injuries to Varane and Martinez, who have both been outstanding this season, have the potential to have larger ramifications. The tie can be salvaged but a quick recovery for the pair is not guaranteed.
Without those two defenders against Nottingham Forest on Sunday, Harry Maguire and Victor Lindelof are set to start. That pair are synonymous with the failed Ole Gunnar Solskjaer era and seeing them together evokes bad memories for some.
Maguire and Lindelof are reliable, but history has shown they're not at the level required to start for Manchester United should the club want to contend for major honours, which is exactly why Varane and Martinez were signed.
They are capable enough to deal with Nottingham Forest, who have scored just 24 goals this season - Everton (23) have scored fewer - but there are doubts about what the defence could look like later this month.
In just eight days, United will make the trip to Wembley again to face Brighton in the semi-final of the FA Cup and Maguire is suspended for that clash, which will leave Lindelof as the only senior centre-back available.
How will that problem be dealt with? Ten Hag was asked about Maguire's upcoming suspension at his press conference and said: "We have to take that in mind as well, we know Harry's suspended but he played very good against Everton.
"Yesterday he played very good and in the coming games it's up to him, but we have to take in mind he's suspended for Brighton."
The most likely solution against Brighton will be playing Luke Shaw at centre-back. Although it was initially a surprise, Shaw has played in that role on a few occasions this season and his performances in central defence were excellent, to his credit.
There are other options, of course, but aren't so appealing. Phil Jones has not been included in a match-day squad since the apportionment of Ten Hag, yet he might be called upon to make the trip to Wembley to face Brighton.
Elsewhere, Teden Mengi could potentially be an option, however, it's understood academy staff have earmarked the Under-21s match against Leicester on Monday as the ideal fixture for his return, as he's not quite at full fitness yet.
Mengi went down with an injury, forcing him to be taken off the pitch on a stretcher, in a friendly against Real Betis as part of United's warm-weather training camp in December and he's not played since.
The final option is Rhys Bennett, who captained the FA Youth Cup-winning side last season. Bennett is an exciting prospect for the future, but he's untested at senior level and throwing him in at Wembley does not seem feasible.
There are four options to solve the crisis, but it would be a shock if changing Shaw's position isn't the answer.
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