The Scottish champions, second in the group behind the 2009 and 2011 winners after two matches, have never managed a win in 12 trips to the Iberian nation, slumping to nine defeats and three draws.
Favourites Barca are unbeaten in 17 European home outings, winning 14, going back to a 2-1 defeat against Rubin Kazan in October 2009.
Their Argentine World Player of the Year Messi, top scorer in Europe's elite club competition the past four seasons, netted his 21st hat-trick for the club on Sunday in a 5-4 La Liga win at Deportivo Coruna.
The unstoppable 25-year-old took his tally in 2012 for club and country to 71, leaving him only four short of the record of 75 set by Brazil great Pele in 1959.
Celtic coach Neil Lennon, who played twice for the club at Camp Nou and came away with two draws, knows the size of the task but said he believes his side is capable of preventing Barca from making it three group wins out of three.
"I'm not saying we're going to go there and get hammered," Celtic coach Neil Lennon was quoted as saying in the Scotsman newspaper on Sunday.
"We're going to try to get something out of the game, but we know how monumentally difficult that will be," he added.
"They can pin you back for long periods but I still want us to have some kind of outlet where we can get a foothold in our attacking half and create chances.
"It's do-able, it's feasible. I've seen Spanish clubs do it and I've seen European teams do it. We'll study a lot of footage and take it from there."
While Celtic are on a high after Saturday's 5-0 drubbing of St Mirren, a performance Lennon described as the team's best of the season, they have a number of injury worries.
Midfielder Kris Commons has a hamstring problem, while Lennon said forward Lassad, who knows Barca well from his stint at Deportivo, was "a major doubt" with a groin strain.
Lennon's Barca counterpart Tito Vilanova has his own selection problems, with a suspension for Sergio Busquets coming on top of injuries to centre backs Carles Puyol and Gerard Pique and right back Daniel Alves.
Although Barca conceded four goals on Saturday for the first time since March 2009 - they were down to 10 men for most of the second half after the dismissal of Javier Mascherano - Vilanova did not seem overly concerned.
"These players, with everything they have won, coming back from international duty and with only 10 on the pitch, they showed the passion they have to keep winning," he told a news conference.
"They showed desire when everything was going against us and I prefer to focus on how much Messi and his team mates ran around after having just returned from playing for their national sides."
Barcelona: 1-Victor Valdes; 19-Martin Montoya, 14-Javier Mascherano, 21-Adriano, 18-Jordi Alba; 6-Xavi, 25-Alex Song, 8-Andres Iniesta; 17-Pedro, 10-Lionel Messi, 7-David Villa
Celtic: 1-Fraser Forster; 2-Adam Matthews, 6-Kelvin Wilson, 4-Efe Ambrose, 21-Charlie Mulgrew; 33-Beram Kayal, 67-Victor Wanyama, 16-Joe Ledley; 88-Gary Hooper; 32-Tony Watt, 7-Nicolas Fedor