Dr. Juvenal Urbino returns home from Paris after years in Europe. While abroad, he recalled his city with fond nostalgia, but when he comes home, he finds his city is a ruin: “Everything seemed smaller to him than when he left, poorer, and sadder…” (102). He lives in his deceased father’s mansion in the old part of town with his widowed mother and aging sisters. Urbino is terrified of cholera and so he has become an expert in the field—his father died trying to fight cholera, and Urbino is dedicated to making improvements to city infrastructure in order to fight cholera. He suggests water treatment, closed sewers, and teaching the poor to build latrines. The people mock him and his ideas, but when cholera disappears from his city, the people thank him.

During this period, Urbino meets Fermina Daza. He treats her for a suspected case of cholera, which turns out to be a mild stomach ailment. After the treatment, the doctor is unable to forget her. He finds ways to return to her house, and he befriends Lorenzo Daza, who wants the doctor to marry Fermina though Fermina hates Urbino and refuses to reply to his many letters.