The Coens won Oscars for writing and directing No Country For Old Men
Burn After Reading, the Coen brothers' black comedy starring Brad Pitt and George Clooney, will launch the Venice Film Festival on 27 August.
The film, about a CIA official whose memoirs fall into the hands of two gym employees, is their first since the Oscar-winning No Country For Old Men.
Recent Oscar-winner Tilda Swinton also appears in the film, alongside Frances McDormand and John Malkovich.
The complete festival line-up will be announced in July.
Pitt was named best actor at Venice last year for his role in The Assassination of Jesse James by the Coward Robert Ford.
Clooney previously worked with Joel and Ethan Coen on the offbeat road movie O Brother, Where Art Thou? and screwball comedy Intolerable Cruelty.
Burn After Reading, the Coen brothers' 13th feature, is scheduled for release in the UK and the US in September.
It is produced by Tim Bevan and Eric Fellner, of British film company Working Title.
The 65th Venice Film Festival will be held from 27 August to 6 September 2008.