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- Marion Cotillard as Dr. Leonora Orantes
- Matt Damon as Mitch Emhoff
- Laurence Fishburne as Dr. Ellis Cheever
- Jude Law as Alan Krumwiede
- Gwyneth Paltrow as Elizabeth "Beth" Emhoff
- Kate Winslet as Dr. Erin Mears
- Bryan Cranston as Admiral Lyle Haggerty
- Jennifer Ehle as Dr. Ally Hextall
- Elliott Gould as Dr. Ian Sussman
- Chin Han as Sun Feng
- John Hawkes as Roger
- Anna Jacoby-Heron as Jory Emhoff
- Sanaa Lathan as Aubrey Cheever
- Demetri Martin as Dr. David Eisenberg
- Armin Rohde as Damian Leopold
- Enrico Colantoni as Dennis French
- Larry Clarke as Dave
- Monique Gabriela Curnen as Lorraine Vasquez