Background: Severe acute pancreatitis is associated with significant morbidity and mortality, often due to systemic complications. Nutritional deficiencies are frequent in this setting, yet neurological complications such as Wernicke’s encephalopathy (WE) remain exceedingly rare. We are a neuropsychiatric syndrome caused by thiamine deficiency, classically linked to alcohol misuse but increasingly recognized in non-alcoholic patients with prolonged fasting, vomiting, or parenteral nutrition. Early recognition and treatment are crucial, as delayed diagnosis is associated with poor outcomes. Case Presentation: We report the case of a 54-year-old woman admitted with severe acute pancreatitis complicated by multiorgan failure. One month later, she developed progressive confusion, ocular abnormalities, and impaired coordination, raising suspicion of Wernicke’s encephalopathy. Neuroimaging supported the diagnosis. Despite supportive management and initiation of thiamine supplementation, the patient’s condition deteriorated, ultimately leading to death. Conclusion: This case illustrates the diagnostic challenges and devastating consequences of Wernicke’s encephalopathy complicating severe acute pancreatitis. Clinicians should maintain a high index of suspicion for this condition in critically ill patients with risk factors for thiamine deficiency. Early empiric thiamine supplementation is a safe and cost-effective preventive strategy that may significantly improve outcomes.