Two giants of the European game struggling to perform in the Champions League do battle at the Wanda Metropolitano on Wednesday, as Atletico Madrid meet AC Milan in Group B.
Diego Simeone's men have just four points to their name from their opening four games, while the Rossoneri are bottom of the rankings with one point from a possible 12.
Match preview
Adding a Champions League crown to last season's La Liga success would have been the ultimate goal for Simeone and Atletico this term, but the Rojiblancos' run in Europe's top tier is at risk of ending before it has even begun.
The Spanish champions were 2-0 down against Liverpool by the 21st minute earlier this month, as Diogo Jota and Sadio Mane struck in a comfortable success for the Reds to leave Atletico's chances of making the knockout rounds in jeopardy.
Simeone's men currently occupy third spot - which would result in an unfancied drop down to the Europa League - in Group B, but second-placed Porto are only one point clear as they prepare to face a daunting trip to Anfield to face the group leaders.
An 87th-minute goal from Felipe saw Atletico claim a narrow 1-0 success over La Liga high-flyers Osasuna at the weekend, but that triumph is only the hosts' second from seven games in all tournaments, so momentum is not exactly on their side.
Atletico have also won just one of their last six games in the Champions League - although it was their dramatic late success over Milan at San Siro - so Stefano Pioli's side will be out for a measure of revenge in midweek.
The last thing that AC Milan and Pioli wanted before a crunch match in Europe would have been a taxing affair ultimately ending in defeat against Fiorentina, but Dusan Vlahovic and co were simply on top of their game to dispatch the Rossoneri in a seven-goal thriller.
The Serbian striker scored twice and set up another on the day as Fiorentina raced into a 3-0 lead, and while a Zlatan Ibrahimovic brace saw Milan threaten a comeback, Vlahovic's second of the day in the 85th minute sealed the deal for Fiorentina and condemn the Rossoneri to their first league loss of the season.
Pioli's side claimed their first point of the 2021-22 Champions League last time out against Porto, but it may be too little too late for the Serie A giants to salvage anything in Europe, as they sit bottom of the rankings and cannot break into the top two no matter what transpires this week.
Milan have now failed to win in three games across all competitions since the start of the month and must welcome runaway leaders Liverpool to San Siro on the final day, so the importance of a first away Champions League win since November 2013 cannot be understated.
Rafael Leao opened the scoring 20 minutes into Milan's meeting with Atletico back in September, but an 84th-minute Antoine Griezmann leveller and Luis Suarez penalty in the seventh minute of injury time left a dumbstruck Rossoneri wondering how they failed to end their losing streak against Atletico - which now stands at three matches.
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Team News
Atletico forward Antoine Griezmann is available again after a second game of suspension was overturned on appeal, but Felipe is banned after seeing red at Anfield.
Suarez played just 25 minutes as a substitute at the weekend but is sure to start this one, while Kieran Trippier is out with a shoulder injury and Joao Felix is doubtful due to a calf issue.
Jose Gimenez will make an immediate return to the defence as Felipe takes his place on the naughty step, with Marcos Llorente potentially starting at right-wing back.
As for Milan, Ciprian Tatarusanu continues to deputise in goal for the injured Mike Maignan, and the Frenchman is joined on the sidelines by Fikayo Tomori, Ante Rebic, Davide Calabria and Samu Castillejo.
Pioli also played down any fears of a serious injury for Leao after the Fiorentina defeat, but Rade Krunic is on standby, and Olivier Giroud may start up top to give Ibrahimovic's 40-year-old legs a rest.
Alessio Romagnoli and Ismael Bennacer could provide fresh legs in defence and midfield respectively, as one of Sandro Tonali or Franck Kessie makes way.
Atletico Madrid possible starting lineup:
Oblak; Savic, Gimenez, Hermoso; Llorente, De Paul, Koke, Lemar, Carrasco; Griezmann, Suarez
AC Milan possible starting lineup:
Tatarusanu; Kalulu, Kjaer, Romagnoli, Hernandez; Kessie, Bennacer; Saelemaekers, Diaz, Leao; Giroud
We say: Atletico Madrid 1-0 AC Milan
Atletico have lost the defensive resilience that made them so formidable under Simeone, but with Griezmann and Suarez linking up in the final third, a depleted Milan rearguard could be in for a long evening.
Both sides have under-performed in this season's tournament, but Atletico have proven a tough proposition at home for most sides in recent weeks and will look to boost their chances of a top-two finish at the expense of the Rossoneri's.
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