It has been a disappointing league season for both sides, Madrid finding themselves fifth in the LaLiga standings, while United sit in fourth in the Premier League. Both sides come into the game on the back of positive results, Atletico easing past Osasuna 3-0, while the Red Devils overcame a spirited Leeds United side 4-2.
Both sides will be hoping for a victory to carry into the second leg, helping aid their pushes for European glory. While not totally out of the question, both teams have an uphill battle to usurp Europe's elite, and United will have one eye on their top-four battle as they look to confirm Champions League football for another year.
Despite not being fit enough to start on Sunday due to illness, World Cup winner Raphael Varane is fit again for selection. The Frenchman will be looking to continue his fine form in a United shirt against Atletico, bitter rivals of his former club Real Madrid.
It once again seems like the Red Devils will be without Uruguayan striker Edinson Cavani, who missed the Leeds game with a groin and stomach issue.
As for the hosts, Brazilian creative midfielder Matheus Cunha missed their matchup with Osasuna and remains a doubt with a knee injury. French superstar Antoine Griezmann was only fit enough for the bench on Saturday, and once again remains a doubt to start for Los Colchoneros. Talismanic midfielder and Atletico captain Koke is also a doubt going into the game.
Atletico Madrid: Oblak, Vrsaljko, Gimenez, Hermoso, Savic, Reinildo, Llorente, De Paul, Herrera, Suarez, Correa
Manchester United: De Gea, Shaw, Maguire, Varane, Dalot, McTominay, Pogba, Fernandes, Sancho, Elanga, Ronaldo
One to watch:
As a Real Madrid legend and a constant thorn in Diego Simeone's side, it is understandable that Atletico faithful have a certain hatred towards the United great. A man for the big occasions, Ronaldo is known for his clutch goals, and he seems to have a particular liking towards beating Atletico Madrid.
As recently as 2019, Ronaldo has taken on Atletico in the Champions League, guiding his Juventus side past them in the Round of 16. The Italian side came into the second leg 2-0 down thanks to goals from Uruguayan pair Diego Godin and Jose Gimenez. However, Ronaldo showed the Madrid side his class as he bagged a hat-trick to carry his side into the quarter-finals.
Going back further than this to his Real Madrid days, the forward dispatched their city rivals twice in the Champions League final. First in 2014, his penalty rounding off a 4-1 extra-time victory for Los Blancos. And then again two years later, this time Ronaldo scoring the decisive penalty in the shootout following a 1-1 draw after 120 minutes of play.
However, it hasn't been a smooth ride for United's number seven following his fairy tale return to Old Trafford in the summer of 2021. The Portuguese hitman endured his longest goal drought since 2009 as he failed to score in six games, before notching against Brighton.
United fans will be hoping for more of the same from their hero on Wednesday, as they hope to turn their disappointing season around. It will be interesting to see who will hold their nerve between two of Europe's most underperforming teams this season. Ronaldo will be a key element for the Red Devils as he looks to continue his Champions League dominance.
Head to Head:
Although two mainstays of European football, Manchester United and Atletico Madrid have only faced off twice in competitive action. Unfortunately for United fans, neither of these have ended in a win for the English side.
Both games took place in the UEFA European Cup Winners Cup in 1991. Atletico Madrid ran out 3-0 winners in the first game, while United could only muster a 1-1 draw in the return match at Old Trafford.
In their first meeting in Champions League history, United fans will be hoping their side can overcome the misfortunes of the past as they head over to Spain. Both sides will be hoping they can carry a lead into the second leg on March 15.
Atletico Madrid 1 - 2 Manchester United
How to watch:
The game will be broadcasted live on BT Sport 2 and Ultimate, with pre-match coverage beginning at 19:00 GMT.