This report delineates the intricate diagnostic journey and therapeutic conundrum presented by a 61-year-old male who exhibited atypical neurological deterioration shortly after lumbar fusion surgery, manifesting clinical and radiological features suggestive of pseudohypoxic encephalopathy, an entity characterized by symptoms mimicking cerebral hypoxia in the absence of a discernible hypoxic insult. Following an initially unremarkable recovery from an elaborate spinal surgery, the patient’s postoperative condition was confounded by a perplexing decline in consciousness, unresponsive to conventional therapeutic interventions and devoid of clear etiological indicators on standard neuroimaging. The subsequent diagnostic odyssey unraveled a cerebrospinal fluid leak as the putative reason, positing a nuanced clinical paradigm wherein the cerebrospinal fluid leak engendered a state mimicking pseudohypoxic brain swelling. This report underscores the clinical challenges and emphasizes the need for an astute diagnostic approach in postoperative patients with unexplained neurological symptoms advocating for a comprehensive evaluation to identify underlying cerebrospinal fluid leaks and mitigate potential morbidity.