Post-orgasmic illness syndrome (POIS) is a rare condition characterized by post-ejaculatory symptoms. Here is reported the first Brazilian POIS patient. Immunological investigation did not confirm the previous hypothesis of a hypersensitivity reaction. Cell immunophenotyping comparing healthy individuals produced evidence of abnormalities not associated to clinical manifestations. The patient was submitted to specific immunotherapy with transient clinical response and was referred to a psychologist but did not demonstrate clinical improvement of symptoms. Therefore, etiology of POIS remains unclear.