Mateo was condemned by the Holy Inquisition five years ago and had to flee the city to save his life. An enigmatic emissary asks him to return to Seville and take Valerio out of town, the bastard son of his friend Germán recently deceased. Fulfilling his promise, Mateo enters Seville clandestinely and takes refuge in the house of an old friend, Luis de Zúñiga. Mateo moves through the underworld of the city until he finds Valerio. When he is about to embark with him on his way to the New World, he is stopped by soldiers of the Holy Inquisition. While the corpse of a man murdered with strange marks appears in what seems a ritual crime.

In exchange for saving his life, Mateo receives the commission from Celso, the Grand Inquisitor, to investigate the death of one of the most prosperous merchants in the city. In this investigation, Valerio becomes Mateo's shadow, helping him at all times. During his investigations Mateo will meet again with Teresa, widow of his friend Germán, turned into a prosperous painter forced to sign with the name of his father to be able to sell his paintings. Recently Teresa has found inspiration with Eugenia, a young prostitute who will act as a model for the painter. Meanwhile, Zúñiga tries to corrupt the Cabildo so that the epidemic of plague that has already entered the city is not made public. The corpse of a murdered girl appears in the river.

From the first inquiries it is determined that the corpse corresponds to Lucina Utrera, daughter of one of the captains of the American fleet. Mateo concludes that the two corpses are related to his old printing press. Mateo suffers insomnia and depressive episodes that make him have a sinister recurrent vision. Teresa decides to hire Eugenia in her husband's silk factory, against the advice of her manager who warns her that all workers are men and only one man can make decisions in the factory. The plague inexorably extends. The father of Leandra, Valerio's girlfriend, and Morata, one of the members of the Cabildo, whom Zúñiga had bought, die. The government is forced to publicize the disease and close the city.

While the plague ravages Seville, Mateo and Valerio find the missing Carmen Galvez, lover of the deceased merchant killed. She informs them that behind the murders is Ledesma, secret leader of the Sevillian Protestants. Zúñiga is appointed a member of the Cabildo to replace Morata and tries by all means to get them to open the port of the city. In the silk factory several workers try to rape Eugenia and Teresa decides to dismiss all those who have participated in the matter. To replace them, he hires several prostitutes chosen by Eugenia. Days later, Teresa is assaulted and humiliated with violence. Another corpse appears, Dresdner, treasurer of the Casa de la Moneda and economic support of Zúñiga. This murder is similar to the previous ones and points in the same direction: Ledesma. Leandra, Valerio's girlfriend, sick with plague.

Mateo is convinced that Germán did not commit suicide. Teresa agrees to unearth him. Zúñiga takes advantage of the plague, hunger and revolts to get the port open and the Indian fleet can arrive. By order of the Cabildo, the silk factory is closed after a confrontation between Teresa and the officials who come to fulfill the order. There must be a man in charge of the business. The union standards are being violated. The investigations of Mateo and Valerio pay off and discover the secret identity of Ledesma. Despite all the care received, Leandra dies. Valerio, full of rage and despair, demands Matthew to keep his word and take him to the New World.

The plague outbreak begins to subside in the city. The Grand Inquisitor gives Mateo his order of freedom. Mateo has solved the case. As a result of the investigation, some Protestants who are diverting precious metals to Flanders to finance the war against the Spanish Empire are arrested by the Inquisition. An auto de fe is celebrated in which the accused are condemned to die at the stake. The Cabildo is inflexible with Teresa. She must appoint a man responsible for the factory, otherwise she will be permanently closed and she will be imprisoned. While the auto de fe is taking place, Mateo discovers that Ledesma was not the real murderer. This certainty will lead Matthew to a desperate action in which he is about to lose his life.