But lets not forget the incredible night in the last round that saw Barca come back from 4-0 down in the first leg to go through.
Dybala was replaced early in the second half of Saturday's 2-0 Serie A win at Pescara after suffering an ankle injury, but he has travelled to Spain in a 23-man Juve squad. If Juventus scores first, Barcelona will find itself needing five goals.
Things have changed since Barcelona's historic comeback against Paris Saint-Germain in the last round of the Champions League. More amazingly, three of their goals were scored in or after the 88th minute.
Luis Enrique said they should stay until the end this time, with the team planning to fight until the final whistle to turn the game around.
'We have nothing to lose. Barcelona has lost three of its seven games since that spectacular victory over PSG at the Camp Nou.
"We have to get to 91 points - Roma can do 90", he said.
The rest of the team is expected to be unchanged from the team that played last week.
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Monaco has already played 53 games in all competitions this season and fatigue is starting to take its toll on the French league leaders. Madrid now sit at the top of the table with a three-point lead and one game in hand. "We need those three points to arrive in the best possible condition".
Leicester had to overturn a one-goal first-leg deficit against a Spanish team in the last 16, and achieved the feat at the expense of Sevilla.
Dybala suffered an ankle injury in Juve's 2-0 victory over Pescara on Saturday, but the Argentina global expects to feature against Barca on Wednesday.
"He's taken a knock and twisted it a little but there's still four days, we have to be optimistic", Juventus coach Massimiliano Allegri said.
"If Juventus eliminate Barcelona, the self-esteem will grow".
Barcelona will get Sergio Busquets back after he was suspended from the first leg.