Methemoglobinemia is a rare cause of hypoxia and can be a diagnostic challenge early in the disease course. The incidence of medication-induced methemoglobinemia is more common than congenital-related methemoglobinemia. The most common cause of methemoglobinemia is exposure to household detergents, illicit drugs, or medications with nitrate or sulfonamide chemical groups. The 2 main medications accounting for up to 45% of medication-induced cases are dapsone and benzocaine. We report a case of hypoxia and diarrhea with an arterial blood gas (ABG) showing methemoglobinemia at 26%. Infectious and autoimmune workup were negative. Methemoglobinemia level returned to normal level within 2 weeks of hydrochlorothiazide discontinuation, suggesting medication-induced methemoglobinemia at appropriate hypertension dosage. In this case, there was an acute rise in methemoglobin levels following initiation of an hydrochlorothiazide-losartan combination, which improved following the discontinuation of hydrochlorothiazide. Extensive workup ruled out cytochrome b5 reductase (Cb5R) and Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which raised the suspicion of hydrochlorothiazide-induced methemoglobinemia, as it is part of the sulfa drug family.