Henrikh Mkhitaryan and Michael Carrick are likely to be unavailable for the EFL Cup final, but Jose Mourinho's main frustration after cruising into the Europa League last-16 was the Football Association's FA Cup scheduling.
Despite Sunday's Wembley date with Southampton looming large, and boasting a 3-0 first-leg lead in St Etienne, the Portuguese plumped for a strong line-up in Wednesday's Europa League last-32 clash.
Mkhitaryan's deft touch secured a 1-0 win in France but progress to the last-16 draw came at a cost for United - and not just because Eric Bailly was sent off in the second half.
Match-winner Mkhitaryan limped off after 25 minutes with a hamstring issue and veteran midfielder Carrick sustained a second-half calf complaint, putting both players' hopes of facing Southampton on Sunday in jeopardy.
"Honestly, I don't think he is fit," Mourinho said of Mkhitaryan.
"I think him and Michael are both out, but this is based on my experience, not based on my medical knowledge and not based on tests and what they have obviously to do tomorrow and after tomorrow.
"I think no chance but I repeat it's just my experience. A calf, a hamstring, even if it is minor, minor, some fibres damaged, I think out."
The injuries compounded doubts over defender Phil Jones and United captain Wayne Rooney, whose future remains subject to intense speculation.
Rooney is highly unlikely to leave for the Chinese Super League before next week's deadline Press Association Sport understands, despite reports that his agent is in China to negotiate a potential deal.
Worries over the quartet's availability for the final against Southampton appeared less of an annoyance than the announcement just before kick-off that the FA Cup quarter-final with Chelsea will be on Monday, 13 March, sandwiched between their Europa League last-16 first and second legs.
Mourinho was perplexed by the decision to announce the date before Friday's European draw and took a shot at the organisers, as well as a swipe at rivals Manchester City after their much-changed side last season lost 5-1 at Chelsea in the FA Cup.
Asked if he was worried the FA Cup scheduling would hinder his chances of progress, Mourinho said: "Of course and I feel really surprised that the decision is made before our draw in Europe.
"Because in this moment nobody knows where we play, nobody knows where the first and second matches are.
"Imagine we play Chelsea on Monday and then we have to go to the second match in Europe in Russia, Turkey or Greece.
"I think once more the interests, they go in front of the clubs and English football's interests, and nobody cares about it. But this is what I have.
"I cannot play against Chelsea with the second team. I cannot play against Chelsea with the under-21s like Manchester City did last year. I cannot do that - we are Manchester United.
"I don't do that as Manchester United manager. I don't do that to the FA Cup because the FA Cup is not guilty of these decisions.
"The FA Cup is beautiful, the competition is historical. I have to treat Manchester United supporters and the FA Cup in the right way.
"I cannot go there with under-21s. Probably they would deserve it, but I don't do that, so what is going to happen is an accumulation of matches.
"People playing a lot of matches, I have to make some rotation but some of the boys will have to play in all these consecutive matches.
"And if situations like the Mkhitaryan one or the Carrick one happen, they happen."