The Europa League final defeat leaves Manchester United out of Europe for only the second time since the ban on English teams was lifted in 1990.
It also means what was going to be a significant summer overhaul takes a different direction. Reports suggest the club have around £100m to spend on new players in the summer, but with £62.5m of that earmarked for Matheus Cunha and the rest potentially going on Liam Delap, the Red Devils will need to offload some players.
The one positive of being out of Europe means the squad shouldn't need to be quite as big, but with United's perpetual injuries woes, Ruben Amorim will likely want a decent-sized squad to help them climb the Premier League table.
While there will be calls for Andre Onana to go, the club have more pressing concerns. United didn't sign a poor goalkeeper, but his form and confidence both seem to have fallen through the floor and the coaching staff will be tasked with restoring him to the goalkeeper they signed from Inter.
They will also have to be very mindful of the money they do spend, with players likely having to leave before more come in.
Below, we look at the first-team players Manchester United should move on in the summer.
Literally any amount of money to get Casemiro's wages off their books will be good business by United. The Brazilian impressively fought his way back into Amorim's plans, but United have little need for two defensive midfielders.
Casemiro has returned to form in recent weeks, although most of his better performances have been in the less physical Europa League, and the physical decline isn't stopping.
While Casemiro has certainly done a job for United in his two seasons at Old Trafford, there's simply no justification for keeping a player on the 33-year-old's substantial wages.
Aston Villa have the option to buy Marcus Rashford for £40m in the summer, and while the forward has certainly impressed at Villa Park, Villa's own financial worries mean that money may be better spent elsewhere.
Should Villa not take up the option to make Rashford's move permanent, the United academy graduate will return to Old Trafford, and while there's still clearly a player there, it doesn't appear his future will be under Amorim, and it's another player with a sizeable salary that could be better spent elsewhere.
While he's not exactly excelled this season, Alejandro Garnacho has shown enough for there to be interest in him across Europe, with Napoli strongly linked back in January.
Per 90 minutes played in the Premier League, Garnacho ranks fourth for progressive carries, fifth for shots, sixth for progressive passes received, sixth for touches in the penalty area and 18th for touches in the final third, all while playing in an atrocious Manchester United side.
It all goes to suggest that Garnacho is a good ball carrier who frequently gets into good shooting positions, though his decision-making often lets him down.
In another league, under another coach in another system, Garnacho has the potential to thrive, but if United can get in excess of £40m for the Argentine, it's worth taking.
If there's one positive from United's transfer dealings, it's been the form of Antony at Real Betis. While his highlight reel is somewhat deceptive, the winger does look more like the player signed at Ajax.
While United fans might wonder why it is that players suddenly look so much worse at Old Trafford than they do elsewhere, the physicality of the league provides much of the answer.
Antony couldn't hack in England and won't be able to next season, but he's shown his ball carrying skills of old that may tempt a European club - potentially even Betis - to make a move.
Depending on the interest, this one may need to be a loan move. Due to Rasmus Hojlund substantial transfer fee, United will need to record a £45m sale just to break even on the books, and based on what we've seen this season, they'd do well to command half of that.
There is definitely a goalscorer in Hojlund, and in a different environment, he has all the tools to score 15 goals for a decent Bundesliga or Serie A side, at which point his resale value could receive a boost, or he may find himself with a future at United again.
But right now the Dane looks like he'd rather be anywhere else doing anything else.