The unnamed narrator is an intellectually curious man who becomes entirely consumed by his admiration for his first wife. He struggles with a tenuous grasp on reality and frequently relies on opium to manage his intense emotions and grief. His narrative perspective dominates the story, and he filters his world through a lens of extreme passion and philosophical obsession.

Ligeia is an extraordinarily intelligent and independent woman. She possesses vast knowledge of metaphysical science and esoteric arts. Her unusual beauty includes an emaciated figure, raven-black hair, and extremely large, dark eyes that captivate her husband. She approaches the world with fierce intensity and expresses her philosophies on mortality through poetry.

Rowena is a cheerful, fair-haired noblewoman who moves into an isolated, gloomy English abbey with her new husband. She embodies conventional societal attributes and remains largely submissive and traditional in her role as a wife. She struggles to understand her husband's dark moods and finds herself increasingly unhappy in the oppressive environment of their new home.