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Postorgasmic illness syndrome (POIS) is a rare and singular syndrome. About fifty cases have been reported in the medical literature. Through a clinical observation, we illustrate the first case diagnosed in Tunisia and the difficulties in the etiological diagnosis and the therapeutic management of this syndrome. Given the shortage of cases reported in the literature, the syndrome of POIS remains poorly identified and subsequently misdiagnosed. The clinical diagnosis is relatively simple, yet etiological and therapeutic questions remain to overcome., Competing Interests: All authors declare that they have no conflicts of interest to disclose., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)