Patient: Male, 43Final Diagnosis: Hepatopulmonary syndromeSymptoms: DyspneaMedication: —Clinical Procedure: —Specialty: Gastroenterology and HepatologyObjective:Unusual clinical courseBackground:Hepatopulmonary syndrome (HPS) is a pulmonary complication of advanced liver disease with dyspnea as the predominant presenting symptom. The diagnosis of HPS can often be missed due to its nonspecific presentation and the presence of other comorbidities.Case Report:We present an interesting case of an obese 43-year-old man who presented with progressive, unexplained hypoxemia and shortness of breath in the absence of any symptoms or signs of chronic liver disease. After extensive cardiopulmonary investigations, he was diagnosed with severe HPS as a result of non-alcoholic steatohepatitis (NASH) leading to cirrhosis. He subsequently underwent successful hepatic transplantation and continues to improve at 12-month follow-up.Conclusions:HPS needs to be considered in the differential diagnosis of unexplained hypoxemia. Given its poor prognosis, early diagnosis is warranted and treatment with liver transplantation is the preferred choice.