- Fermina Daza – Florentino Ariza's object of affection, and wife of Dr. Urbino, very beautiful and intelligent.
- Dr. Juvenal Urbino – highly respected, wealthy doctor and husband of Fermina Daza.
- Florentino Ariza – businessman who is in love with Fermina Daza.
- Lorenzo Daza – Fermina Daza's father, a mule driver; he despised Florentino and forced him to stop meeting Fermina. He is revealed to have been involved in some illicit businesses to build his fortune.
- Jeremiah de Saint-Amour – The man whose suicide is introduced as the opening to the novel; a photographer and chess-player.
- Aunt Escolástica – The woman who attempts to aid Fermina in her early romance with Florentino by delivering their letters for them. She is ultimately sent away by Lorenzo Daza for this.
- Tránsito Ariza – Florentino's mother.
- Hildebranda Sánchez – Fermina's cousin.
- Miss Barbara Lynch – The woman with whom Urbino confesses having had an affair, the only one during his long marriage.
- Leona Cassiani – She starts out as the "personal assistant" to Uncle Leo XII at the R.C.C., the company which Florentino eventually controls. At one point, it is revealed that the two share a deep respect, possibly even love, for each other, but will never actually be together. She has a maternal love for him as a result of his "charity" in rescuing her from the streets and giving her a job.
- Diego Samaritano – The captain of the riverboat on which Fermina and Florentino ride at the end of the novel.
- América Vicuña – The 14-year-old girl who toward the end of the novel is sent to live with the elderly Florentino; he is her guardian while she is in school. They have a sexual relationship, and after being rejected by Florentino and failing her exams, she kills herself. Her grooming and subsequent suicide provides a counterpoint to the novel's grand romantic themes.
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