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- Bill Murray as Steve Zissou
- Owen Wilson as Edward "Ned" Plimpton
- Cate Blanchett as Jane Winslett-Richardson
- Anjelica Huston as Eleanor Zissou
- Willem Dafoe as Klaus Daimler
- Jeff Goldblum as Alistair Hennessey
- Michael Gambon as Oseary Drakoulias
- Bud Cort as Bill Ubell
- Noah Taylor as Vladimir Wolodarsky
- Seu Jorge as Pele dos Santos
- Robyn Cohen as Anne-Marie Sakowitz
- Waris Ahluwalia as Vikram Ray
- Matthew Gray Gubler as Nico
- Isabella Blow as Antonia Cook
- Seymour Cassell as Esteban du Plantier