- Kirsten Raymonde – Is a young child actor from Toronto who is eight when the Georgian flu destroys her world. Initially she and her brother are the only survivors in her family but as they travel he dies too. She joins the theatre troupe as a teenager and becomes obsessed with actor Arthur Leander, whose death she witnessed as a child.
- Arthur Leander – A wildly successful film actor originally from the fictional Delano Island in British Columbia. Despite his success Arthur is shiftless and unhappy and marries three times. He dies onstage of a heart attack portraying King Lear in a Toronto theatre at age 51 the night the pandemic takes hold of North America.
- Jeevan Chaudhary – A former paparazzo, turned entertainment journalist, turned EMT whose life keeps intersecting with Leander's at key moments.
- Frank Chaudhary – Jeevan's veteran disabled brother, a ghostwriter who lives a life of solitude in his apartment.
- Miranda Carroll – Arthur's first wife who is eleven years younger than him. She is both an artist who is obsessed with creating her graphic novel, Station Eleven, about Dr. Eleven, a man who lives on a space station shaped like a planet that evacuated when aliens descended, and a proficient business woman. Shortly before Arthur's death, Miranda gives him copies of her finally completed graphic novel which Arthur later gives to Kirsten and his son, Tyler. Mandel has said this is the character of her creation she most identifies with.
- Clark Thompson – Arthur's British best friend whom he met while they were struggling actors who later works as a corporate businessman and then after the collapse of civilization reinvents himself as a curator to a museum dedicated to obsolete objects.
- Tyler Leander – The son of Arthur and his second wife Elizabeth. He grows up in Jerusalem and is stranded in an airport in the fictional city of Severn for two years after the epidemic. He and his mother eventually leave with a religious cult and he grows up to be the religious leader known as the Prophet.
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