Encephalopathy has been frequently reported in patients with acute respiratory distress syndrome (ARDS) related to COVID-19, and its etiology remains undetermined. These patients display hypercatabolic state, weight loss, use of diuretics, and dialytic therapy, which represent risk factors for thiamine depletion. The diagnosis of Wernicke encephalopathy (WE) is challenging and based on risk factors for the depletion of thiamine. We reported three cases of patients with COVID-19-related WE treated with intravenous thiamine. All patients responded with immediate neurologic improvement, and two of them had accelerated ventilatory weaning. The cases reported suggest that thiamine deficiency could represent relevant etiology of COVID-19-related encephalopathy.