Despite the many advancements in liver transplantation (LT), mortality in patients with hepatic failure remains high, and to date, many patients die while awaiting LT. The molecular adsorbent recirculating system (MARS®) is an extracorporeal liver support system intended to provide short-term metabolic detoxification, often as a vital bridge to LT. We report the case of a 41-year-old non-Hispanic White male who developed worsening multi-factorial encephalopathy in the setting of decompensated alcoholic cirrhosis. He continued to deteriorate despite supportive medical therapy, and extensive investigation for alternative causes of encephalopathy aside from hepatic was unrevealing; as a result, there was concern that his encephalopathy was due to irreversible causes from which he may not recover appropriately following LT. We herein: i) describe the implementation of MARS as a diagnostic intervention for encephalopathy of uncertain etiology in a patient with end stage liver disease who, on the basis of prompt psychomotor improvement, underwent LT 19 days post-MARS implementation with an excellent clinical outcome and thus ii) propose the use of extracorporeal liver support not only as a short-term bridge but also as a diagnostic (and potentially therapeutic) measure in cases of cryptogenic encephalopathy, particularly in the setting of advanced liver disease.