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- Jennifer Aniston as Justine Last
- Jake Gyllenhaal as Thomas "Holden" Worther
- John C. Reilly as Phil Last
- John Carroll Lynch as Jack Field
- Tim Blake Nelson as Bubba
- Zooey Deschanel as Cheryl
- Mike White as Corny
- Deborah Rush as Gwen Jackson
- Aimee Garcia as Nurse