Though Atletico's the team at home, it's Barcelona that's favored in the soccer betting odds. The Catalan giants are listed in the +115 to +125 range to win, with the Mattress Makers at +250 or so and a draw at the same kind of price.
Four days after earning that 1-1 draw in the first leg at the Nou Camp, Atletico was tasked with another difficult fixture at home to Villarreal.
The visitors made the Mattress Makers work throughout, but the hosts' extra bit of a quality, this time through Raul Garcia, resulted in a 1-0 victory. There were only four total shots on goal between both teams.
The win kept the top three of La Liga the same, with Atletico top of the table on 79 points, Barcelona one point behind and Real Madrid three back.
Unfortunately, bad news in the form of an injury to star striker Diego Costa put a damper on that draw in the first leg. Costa strained his thigh at the Nou Camp and missed Atletico's match against Villarreal as a result. His status for Wednesday is still up in the air, but it's not looking good.
Should Costa miss out, the Mattress Makers are going to need even more support from their supporters. They've done the job so far, helping Atletico go undefeated (14 wins, three draws) in 17 league fixtures at home.
Barcelona didn't let the home draw get to them, as they responded with a comfortable 3-1 win over Real Betis over the weekend.
Messi scored two goals, with the other goal coming from a Betis own goal. The Catalans weren't anywhere near their best, yet still managed to get the three points with little resistance coming their way.
The victory, as we mentioned above, kept Barcelona within striking distance of Atletico for the summit of La Liga.
Now it's time for the Catalans to put their entire focus into the Champions League. They're not in the best of spots after an unconvincing display in the first leg, but if there's any team you expect to find their way, it's Barcelona.
In Europe so far this season, Barcelona has beaten the likes of Manchester City (2-0) and Celtic (1-0) away, while drawing with AC Milan (1-1) and losing to Ajax (1-2). Will they come out and dominate proceedings on Wednesday?
Champions League Pick
This is an incredibly hard match to predict.
The Catalans should enjoy the majority of possession, but that didn't exactly work out too well in the first leg, with Atletico looking mighty dangerous on the counter, with Costa looking frightening whenever he had the ball. Whether or not Costa suits up remains to be seen.
We can't lose sight of how dominant the Mattress Makers have been at home either. They've still yet to lose a league match on their own pitch and you know the atmosphere is going to be even crazier with so much on the line on Wednesday.
Still, we can't shake the feeling that Barcelona will find a way. The potential absence of Costa would be huge, and we can't forget just how good the likes of Messi, Iniesta and company really are. We're taking the Catalans to emerge victorious in what should be a dogfight until the end.
Pick: Atletico Madrid 1 Barcelona 2
Aggregate: Atletico Madrid 2 Barcelona 3