Corinthians are well placed to reach the quarter-finals after securing a 0-0 draw in Ecuador last week but they must overcome the enormous expectations of their fans as well as their opponents.
Corinthians are the only one of Sao Paulo's big four clubs yet to win South America's premier club competition and the pursuit of the trophy is an obsession with supporters, players and backroom staff alike.
"It is exciting - for those who like football and those things that only football can provide - to see the intensity with which Corinthians fans live and die in the Libertadores," columnist Mauricio Oliveira wrote in sports newspaper Lance.
"The growing obsession... deserves to be studied by sociologists, psychologists and parapsychologists, mystics, sceptics and others," he added.
Corinthians fans, known as 'The Faithful', are some of the most passionate in Brazil.
Their team have already been world club champions, having won the inaugural Club World Cup in Brazil in 2000.
European giants Manchester United and Real Madrid came to compete but it was Corinthians who beat fellow Brazilian side Vasco da Gama on penalties to claim the trophy.
However, that boast is largely a defensive mechanism against the taunts of their more successful rivals.
Santos and Sao Paulo have each won the Libertadores three times and Palmeiras once. Libertadores memories are bitter ones for Corinthians fans, who have never seen their team get past the semi-finals.
The toughest exit came in 2000 at the hands of their most bitter rivals Palmeiras.
The teams were deadlocked at 6-6 after two pulsating semi-final legs but Palmeiras qualified for the final on penalties when Corinthians idol Marcelinho Carioca missed the last and deciding spot kick.
The most memorable elimination came in 2006 when Corinthians went out at home in the quarter-finals against River Plate of Argentina.
With Argentines Javier Mascherano and Carlos Tevez in their ranks, Corinthians were favoured to overturn a 3-2 deficit from the first leg.
Instead they went down 3-1 amid sensational scenes at Pacaembu stadium. Irate fans invaded the pitch, causing an upheaval that prompted the police to intervene.
The most embarrassing defeat, though, came last year when a team featuring Ronaldo and Roberto Carlos were knocked out in the preliminary stage by Colombian club Tolima.
Roberto Carlos ended up leaving Corinthians after being threatened by angry fans.
Despite the Libertadores setbacks, Corinthians players say they feel no extra pressure heading into this week's match.
Winning the Libertadores "is the dream of any Corintiano," said striker Liedson, "but it isn't despair or obsession.
"I knew all about the responsibility when I came here. But playing for Corinthians is always a big responsibility. We know what we have to do. We just need to be focused."
Such is the pressure, though, that everyone involved with the team has trouble maintaining that focus.
The players, the manager and even the club president all went ballistic at the referee in last week's first leg in Ecuador, even though he made no calls that affected the result.
Even hardcore fans agreed that reaction was over the top and pleaded with the team to keep their cool.
"The weight of the shirt, a capacity crowd, never having won the trophy before, it plays with their heads," said Nader Ghobar, a Corinthians fan who was buying a ticket for Wednesday's match.
"Everyone is anxious and excited. The pressure is really on and you can see it makes a difference."