Lyon left to regroup for Champions League bid after painful European exit
Paulo Fonseca's side came from 2-0 down at Old Trafford to lead 4-2 in extra time, and 6-4 on aggregate, in their Europa League quarter-final despite being reduced to 10 men late in normal time.
But the English club somehow fought back again late in extra time to level the tie once more before Harry Maguire got their winner in the 121st minute.
That denied Lyon a first European semi-final since they got to the last four of the Champions League in 2020, and they have to now hope the manner of their elimination does not have a knock-on effect for the remainder of their domestic campaign.
"At 4-2, with 10 minutes left, I think we thought it was done. It hurts," Corentin Tolisso, who was sent off for a second booking, told broadcaster Canal Plus.
"It is one of the worst matches in my career. It is really, really tough. I think we deserved better. Now we need to pick ourselves up and digest this because we have a match on Sunday that we absolutely have to win."
Lyon were once Champions League regulars but have not graced Europe's elite club competition since 2020, when they lost to Bayern Munich in the last four behind closed doors in Lisbon.
Their precarious financial position makes playing in the highly lucrative Champions League all the more important for the seven-time French champions.
American owner John Textor sacked popular coach Pierre Sage in January and replaced him with Fonseca because he felt the Portuguese former AC Milan boss was more likely to lead the team to a top-four finish in Ligue 1.
Textor then gave his backing to the new manager after Fonseca was handed a nine-month ban from the touchline and the changing rooms during games following an angry altercation with a referee in a match against Brest in early March.
Lyon have won seven of 10 Ligue 1 outings under Fonseca, including five of their last six, and ended last weekend fourth in the table.
There are five games left, starting with Sunday's trip to fierce derby rivals Saint-Etienne, who are fighting relegation.
Only the top three qualify directly for the Champions League, with the team in fourth entering in the preliminary rounds.
Lyon are a point behind Marseille in third, but also lie just three points clear of Nice in seventh, which may not be enough to qualify for Europe at all. The pressure is therefore on.
"We did magnificent things, showed the quality of our players, but we need to learn from this," Fonseca said after the defeat at Old Trafford.
"It is not easy to come here. I think we proved that we are ready to have an end to the season which matches our ambitions and our quality."
Player to watch: Ousmane Dembele
The Paris Saint-Germain star is hoping to end the season as Ligue 1's leading scorer after his transformation in recent months which has seen him become one of Europe's most clinical finishers.
Dembele has 32 goals in all competitions, and 21 in Ligue 1. He needs six more from PSG's final six matches to equal Kylian Mbappe's top-scoring tally of 27 last season. The former Barcelona winger will hope to get among the goals against struggling Le Havre on Saturday and in Tuesday's trip to Nantes.
Key stats
10 - PSG can make it 10 straight Ligue 1 wins if they beat Le Havre, a feat they have not achieved inside the same season since winning their first 14 games of the 2018/19 campaign
10 - Montpellier have lost their last 10 games. Their relegation could be confirmed this weekend
5 - The number of points separating six teams, from Monaco in second to Nice in seventh, in the fight for European qualification
Fixtures (times GMT)
Friday
Rennes v Nantes (1845)
Saturday
Paris Saint-Germain v Le Havre (1500), Monaco v Strasbourg (1700), Marseille v Montpellier (1905)
Sunday
Lille v Auxerre (1300), Nice v Angers, Brest v Lens, Reims v Toulouse (all 1515), Saint-Etienne v Lyon (1845)