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Plague epidemics have remained in the collective consciousness until nowadays remembered as the deadliest. Therefore, it is not surprising that the answers to them throughout history have been not only medical but also religious. The previously mentioned will be analyzed in this paper through the cults of the protector saints against the plague epidemics that have developed in two Croatian cities of comparable size, Rijeka and Osijek, but with the diametrically opposed geographical positions and, accordingly, quite different historical developments. On the one hand, a more detailed overview of the development of the cults of various saints present in the mentioned cities will be presented. On the other hand, based on their presentation in the sacral heritage of these cities, the broader context of the time and space in which they have developed will be lightened. Particular attention will be paid to their medical connotations. [ABSTRACT FROM AUTHOR]