The English side have won only six points from their opening six Premier League fixtures, and that's their worst league start since 1986 (four).
United have never beaten Atleti in official competition
Indeed, since both teams last played their first match in this season's UCL, Atleti have won all four of their games, whilst United have drawn two and lost two.
The energy that Diego Simeone will insist his players bring into the game means that unless the visitors are willing to match them for effort and commitment, this could be a very long night for Michael Carrick and his side.
In four official games against Atleti, United haven't won any, drawing two and losing two more, though the hosts have only won two of their last 15 games against English sides (D3 L10).
The only club that the Red Devils have faced five times in UEFA competition without winning is another Spanish outfit, Sevilla (D2 L3), and it's also worth pointing out that Atleti have let in at least one goal in 14 of their 15 home European matches since the beginning of 2024.
Atleti's one win against English opposition in last five
Five of the last seven UCL fixtures for the Spaniards have seen them face English opposition, and they've only managed one win in those matches, though more generally, they did win five of their eight home UCL games in 2025/26, and scored 22 goals.
United might also take heart in the fact that their opponents have already lost their only UCL game this season to the Red Devils' big rivals, Liverpool, as well as the knowledge that United themselves have lost just one of their last 11 games against Spanish opponents (W7 D3).
Taking the blueprint from the way the Reds approached that game and adapting it to fit might not be the worst idea in the world for a side that are currently languishing in 13th place in the Premier League.
Already without Benjamin Sesko and Patrick Dorgu, the United manager could also lose the services of Kobbie Mainoo and Luke Shaw, both of whom appear to be carrying knocks from their participation in the match against Tottenham.
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Carrick could be forced to count on youngsters
Noussair Mazraoui and Matthijs de Ligt are likely to be sidelined too, increasing the pressure on the Red Devils to get a win against a team that beat them 1-0 in this competition at the Theatre of Dreams back in 2022.
To give further context as to some of the difficulties they could face, if none of the above-named players is fit enough to contribute, Carrick will need to put youngsters Shea Lacey, Harry Amass and Jack Fletcher in the squad, and may even need to call upon their services at some point.
Carlos Baleba's recent debut might put him into contention to replace Mainoo, with both Mason Mount and Andrey Santos available if required.
By contrast to Carrick's woes, Simeone has a fully fit squad to choose from, and with the furore over Julian Alvarez's proposed move to Barcelona not even being enough to derail his team's start to the season, the Spaniard's are likely going to take some stopping on Tuesday night.
Alvarez and Fernandes could be key for their teams
Alvarez has 17 goals in 26 Champions League games for his current club, which includes 10 in 13 at home.
Whether Simeone plays the Argentinian from the start, or prefers either Alexander Sorloth or Jonathan David to lead the line, is a moot point.
All three are capable of grabbing a goal or two, and against a patched-up opponent, they're likely to do just that.
If the visitors can upset the form book and head back to Manchester with a victory, it will be only the third time since Sir Alex Ferguson's retirement that United have begun a Champions League campaign with consecutive wins - and the confidence that would bring might well kick-start their 2026/27 season.
Bruno Fernandes, as always, will be vital to a United victory, though Bryan Mbeumo and Matheus Cunha - against his old side - need to be on song and ready to silence what's expected to be a raucous crowd at the Metropolitano.