Clooney, 50, beloved by his peers and regarded as the most eligible bachelor in the world, is thought to have the edge for his performance as a back-up dad forced to pull his family together in the emotional drama "The Descendants".
But don't count out Dujardin, the French star of silent movie "The Artist", who has happily been spoofing himself and his Hollywood newcomer status on U.S. sketch show "Saturday Night Live" and comedy video website Funny or Die.
"Clooney is in top form and this film, most people felt was the performance of his career," said Tom O'Neil of awards site TheEnvelope.com, noting that Clooney had been campaigning hard in the run-up to the February 26 Academy Awards ceremony.
Clooney won the Golden Globe last month, and has an Oscar under his belt for his supporting role in the 2005 film "Syriana".
But that could work against him. "It's still fresh in people's minds and he's relatively young and still has a career ahead of him. People remember that, and they rarely give Oscars in quick succession," said Stephen Galloway, executive editor of features at industry publication The Hollywood Reporter.
Dujardin, 39, has the opposite problem. A household name in France but unknown in Hollywood, Dujardin utters just two words as silent movie icon George Valentin, who refuses to embrace the talkies in "The Artist."
Nevertheless, he has won a Golden Globe and Screen Actors Guild award for the role and has been the face of "The Artist"s Oscar campaign. If he wins on Sunday, Dujardin would be the first French-born actor to win the Oscar for a lead role.
"This is one of those rare situations where the performance is as good as movie, or maybe even carried the movie, but we don't know if that's just the way Jean is and this is the one performance he can give," said Galloway.
Dujardin rose to fame in France as a comic actor, starring in the television series "A Guy and a Girl," and the 2005 spoof surfer movie, "Brice de Nice" in which he played a dead-beat surfer obsessed with the late Patrick Swayze's character Bodhi in "Point Break."
But some industry-watchers feel he may be too green for the best actor award, and the memory of Italian actor Roberto Benigni, who charmed Americans in 1999 for "Life is Beautiful" and promptly went back to work in Italy, is still fresh.
"Jean Dujardin is part of the crazy moment that 'The Artist' has, but is he the Roberto Benigni type? He has his one big year and is honored for it, but that's the last we hear from him?" said Yahoo! Movies executive producer Sean Phillips.
British actor Gary Oldman, star of thriller "Tinker Tailor Soldier Spy", and Mexico's Demian Bichir, recognized for playing a Los Angeles gardener in an immigration battle in "A Better Life", are regarded as having only outside chances of taking the Oscar home.
And Pitt, who won over audiences with his performance as baseball manager Billy Beane in "Moneyball", may have to wait his turn.
Pitt, 48, is yet to win an Oscar and has only been nominated twice before during a prolific film career that started with him being perceived as a "bit of a rascal", according to O'Neil.
"There's a feeling there for Pitt that he's way overdue and that this movie needs some awards love," said O'Neil.
"Now he's settled down with Angelina (Jolie) and had kids...and there's a feeling that he's adored as a star that matters...an Oscar would be the perfect timing right now."
Pitt also starred in Terrence Malick's mystical "The Tree of Life", which won the top prize at the Cannes Film Festival, and is among the Academy Award best picture nominees.
But Galloway feels Pitt is still too young for the award, despite his body of work.
"He looks younger than he is, he doesn't look like a veteran, and also, he hasn't yet done a body of work that is so significant, although he is putting that together. "Moneyball" will help consolidate that," said Galloway.
