Objective <p>Acute neurological deficits following lumbar microdiscectomy are most commonly attributed to surgical complications. In this study, we present a case of multiple sclerosis (MS) relapse mimicking a postoperative surgical complication.</p> Case <p>A 42-year-old female developed acute left lower extremity plegia in the early postoperative period following L4–5 microdiscectomy. Imaging studies and surgical re-exploration revealed no evidence of a compressive pathology. During clinical follow-up, neurological involvement progressed to the upper extremity. Detailed medical history revealed a prior diagnosis of MS and discontinuation of disease-modifying therapy. Due to contraindication to corticosteroid therapy, therapeutic plasma exchange was initiated, resulting in complete neurological recovery within 48&#xa0;h.</p> Conclusion <p>In the presence of negative imaging findings and anatomical incongruity, MS relapse should be considered in the differential diagnosis.</p>