Anything less than a quick return to form after their 2-0 defeat in the first leg in Milan on Feb. 20 will probably see Barcelona follow Manchester United, who they beat in the 2009 and 2011 finals, through the exit door.
Arsenal, who lost to Barcelona in the 2006 final, are also expected to be eliminated unless they can overturn their 3-1 defeat against German champions-elect Bayern Munich at the Allianz Arena.
The Round of 16 will be completed this week with Schalke 04 going into their home leg against Galatasaray as favourites to advance after drawing 1-1 in Turkey and Malaga seeking to maximise home advantage in their attempt to overturn their 1-0 defeat at Porto in the first game.
If Barca are to join arch-rivals Real Madrid, Borussia Dortmund, Juventus and Paris St Germain, who all made it through to the quarter-finals last week, they need to rediscover the kind of football that has been the envy of Europe for the last six years.
Many observers though, have written off their chances with the Sunday Times in London saying: "Barcelona will presumably secure the Spanish league championship... but the sense grows that the light has dimmed, the magic has faded and the era of glory is over."
That obituary may be a little premature but two defeats to Real Madrid, in the King's Cup and La Liga while coach Tito Vilanova undergoes treatment for throat cancer, has not strengthened the belief that Barcelona can see off Milan.
Barca's assistant coach Jordi Roura rested Lionel Messi and five of his Spain internationals for their 2-0 win over bottom-of-the-table Deportivo La Coruna in La Liga on Saturday, but Messi showed he had not lost his touch when he came off the bench and scored for a world record 17th successive league match.
The resurgent Alexis Sanchez had nodded Barca in front in the 38th minute.
"The team played very well defensively," Roura told a news conference.
"We managed to keep a clean sheet and for us that's important. It helps us ahead of the match on Tuesday."
Milan, the seven times European champions, are on the crest of a wave following their surprise win over Barcelona in the first leg although they are stretched upfront for the trip to the Nou Camp.
Mario Balotelli is ineligible after playing for Manchester City in the group stage and Giampaolo Pazzini is out after limping off with a leg injury in Friday's 2-0 win over Genoa.
Stephan El Shaarawy is likely to lead the line for a side who have rocketed up to third place in Serie A after a superb run of form and fancy their chances of progressing on aggregate against mighty Barca.
"We are going to have to play better in Barcelona than we did at home," Milan boss Massimiliano Allegri told reporters.
Another team enjoying a two-goal advantage going into the deciding leg are
Bayern Munich, last year's runners-up, will also carry a two-goal cushion into the deciding leg after outplaying Arsenal in London.
Manager Arsene Wenger, recognising the enormity of the task his men face, said Arsenal would have to "gamble a little bit" on Wednesday. His observation was something of an understatement as they need to score at least three goals in order to save the tie.
With Borussia already through and Bayern virtually there, Schalke, who will be without the suspended Jermaine Jones, can make it three German teams in the last eight if they see off Galatasaray.