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Abstract: Background: Polyserositis (PS) is the inflammation, with effusion, of different serous membranes. It has been associated with different aetiologies, but the aetiology of PS remains unknown in a high percentage of patients. Aims: The general objective of this retrospective study was to analyse the aetiology of PS cases seen at Son Llàtzer Hospital in an 11‐year period. Other objectives were to determine the epidemiological, clinical and analytical characteristics of these patients. Methods: An observational, descriptive and retrospective study to analyse the aetiology of PS cases seen at Son Llàtzer Hospital. The inflammation of two or more serous membranes confirmed by an imaging test was required and at least one of the serous fluid should be an exudate. Results: A total of 92 patients was included in the study. The most common diagnosis was neoplasm (nearly one‐third of cases) followed by infectious and autoimmune diseases. PS aetiology was unknown in more than one‐third. Pleura and pericardium were the most common sites of serosal involvement (83%). Antinuclear antibodies’ positivity in serum and increased levels of adenosine deaminase in pleural effusion were significantly associated with a final diagnosis of autoimmune disease. Increased pleural lactate dehydrogenase levels were significantly associated with a final diagnosis of neoplasm. In 9 of 14 patients with a previous cancer, PS represented a recurrence of their cancer. Cases of unknown aetiology presented most frequently as pleural and pericardial involvement, and the majority resolved. In very few patients, an infectious aetiology could be proven. Conclusion: PS is a frequent clinical entity that is associated with different diseases and its diagnosis could be challenging, with a high rate of unknown aetiologies. [ABSTRACT FROM AUTHOR]