Postorgasmic illness syndrome (POIS) is a rarely described syndrome characterized by transient flu-like symptoms and cognition disorders. Recent studies suggest that immunogenic reactivity to autologous semen is the underlying mechanism in POIS. Our study is regarding a 30-year-old that visited our unit for an allergy consultation because he experienced malaise after ejaculations. Skin prick tests and intracutaneous tests with autologous diluted semen with negative results were performed. Immunoblotting and western blot of the patient\'s autologous semen showed negative results. To complete the study, we intended to rule out other possible causes such as urological, hormonal, or neuropsychiatric disorders. We present a case of POIS based on the clinical criteria that did not show an IgE mediated cause. In the case of our patient, we could not identify the underlying cause; however, we believe that the possible involvement of neurobiochemical mediators should be studied.