A 29-year-old man was admitted to the hospital in a state of reduced consciousness with new-onset diabetes and positive for coronavirus disease 2019. He presented with severe ketoacidosis and profound hypokalemia. While his diabetic ketoacidosis was promptly corrected, it proved extremely difficult to maintain normokalemia. For a total of 49 hours, not less than 1127 mmol of i.v. Addex-potassium (potassium hydroxide and dipotassium phosphate trihydrate; ∼ 25 mmol/hour) in addition to 76 mmol/d of oral potassium was required, ie, tantamount to doses used to achieve cardioplegia. Severe, sustained, treatment-resistant and potentially lethal hypokalemia may thus occur in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and should be actively monitored. Based upon these findings and converging evidence in the literature, we propose a model in which disruption of angiotensin-converting enzyme 2 by SARS-CoV-2 activates the angiotensin-II pathway, thereby enhancing aldosterone production. Excess aldosterone activates renal epithelial sodium channels, thus promoting massive loss of potassium through urinary excretion. This implies that severe hypokalemia by SARS-CoV-2 infection may be amenable to treatment with potassium-sparing drugs antagonizing the aldosterone receptor, such as spironolactone or eplerenone, whereas potassium supplementation even in very high doses may be futile.