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- Jim Carrey as Lloyd Christmas
- Jeff Daniels as Harry Dunne
- Laurie Holden as Adele Pichlow
- Kathleen Turner as Fraida Felcher
- Jennifer Lawrence as Young Fraida Felcher
- Brady Bluhm as Billy
- Steve Tom as Dr. Pichlow
- Rachel Melvin as Penny Pichlow
- Rob Riggle as Travis and Captain Lippencott
- Lauren Henneberg as Dr. Erinn Knight
- Cam Neely as Sea Bass
- Taylor St. Clair as Mrs. Stainer