Klinefelter syndrome is the most common congenital abnormality causing primary hypogonadism and predisposing to a state of hypercoagulability. We report the case of a 37-year-old man, of Algerian nationality, diagnosed with Klinefelter syndrome admitted to the hospital via the emergency room for acute chest pain and dyspnea. The patient arrived in Tunisia 36 hours ago. On admission, body temperature was 38.2°C, blood pressure, pulse and respiratory rate were 130/70 mmHg, 120/minute and 26/minute, respectively. He had an oxygen saturation of 87% in room air. His electrocardiography revealed a complete right bundle-branch block, chest X-Ray was normal. In front of the clinical presentation and the origin of the patient coming from an endemic country, COVID-19 infection was suspected but ruled out by pharyngeal swabs testing negative by real-time reverse-transcription polymerase chain reaction test and massive pulmonary embolism was diagnosed from his chest computed tomography images. The symptoms improved with anticoagulation treatment.