On the fourth day of the journey, the ship runs out of fuel and is stranded for nearly one week. Florentino realizes the environmental destruction which has ravaged the river and its shores. Finally, he and Fermina attempt to make love. Florentino tells her that he has remained a virgin for her, and though she does not believe it, she likes the spirited way in which he says it. The attempt, however, fails when Florentino, in his old age, cannot perform. But he returns later that day, and makes love to her, though it is "hurried and sad." This disappointment, however, does not hinder their relationship.
When the ship docks at its final port, Fermina is distraught when she recognizes many of the passengers who board the ship, for if she is seen on a pleasure cruise with a man, it will cause a scandal. Florentino uses his power as President of the riverboat company to appease Fermina, and, in writing, orders the Captain, who obeys without argument, to reject all of the oncoming passengers on account that someone aboard has contracted cholera. The captain raises the flag of cholera to alert other ports, and only Florentino, Fermina, the Captain, and his lover remain aboard. Because of the supposed cholera epidemic on board, no port will allow them ashore, and their scheme forever exiles them to the river.
The name of the ship Florentino and Fermina journey on, the New Fidelity signifies the renewed bond of trust and affection between them. Fermina is excited by the prospect of traveling aboard the ship with only the bare minimum of her belongings because the journey will provide her with an escape from her home, full of frivolous trinkets, memories of her dead husband, and his clothes, books, and other belongings. Aboard the ship, she can leave behind her duties as a mother, her social and domestic responsibilities, and the two unbearable scandals revealed on the pages of the Justice, and with them, the shame they have brought to her reputation. When, after Florentino has left her ship cabin, Dr. Urbino's ghost appears to Fermina and tips his hat, she feels appeased and relieved, for her husband's gesture, whether real or imagined, signifies his final farewell to her, and grants her strength to go on without him, and to continue her affair with Florentino.
The novel continues to compare love to an enduring plague in the final chapter. So that Florentino and Fermina may at last be together, Florentino orders the Captain to falsely announce that there is at least one passenger aboard the ship who has been infected with cholera. When interpreted symbolically instead of literally, this statement is mostly true. Florentino has been infected by a burning, unshakable passion for Fermina since the day she rejected him in the Arcade of the Scribes, a passion that has persisted much like a deadly plague of cholera. Florentino is literally plagued by love; he suffers from lovesickness as one would suffer from cholera, enduring both physical and emotional pains, and visible symptoms of his illness. When the Captain raises the yellow flag of cholera to the top of the ship's mast, his action is symbolic of Florentino's surrender to his disease. At long last, Florentino has surrendered to Fermina's love, just as a sufferer of cholera surrenders to death.
The final chapter also explores the concepts of self-sacrifice and death in the name of love. For many years, Florentino has suffered in anguish from his unrequited love. Now that his love is returned, he feels ready to die. Florentino's willingness to die reveals that it is not the experience of Fermina's love—but rather the quest to obtain that love—that has given his life meaning.