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Background: Therapeutic epidural spinal injections (ESIs) of steroids are one of the most common nonsurgical management modalities employed for alleviating pain due to chronic persistent lumbar spinal disease. However, it is well documented that they have significant risks and complications without any long-term efficacy. ESI may result in epidural empyema which may be difficult to diagnose with delays resulting in significant permanent neurological sequelae., Case Description: A 45-year-old female presented with a lumbar spinal epidural empyema after receiving ESI for low back and right leg pain due to a lumbar disc herniation. Laboratory studies showed elevations of multiple inflammatory markers, and the MR documented a significant lumbar epidural empyema contributing to significant thecal sac compression. Clinically, the patient had an acute cauda equina syndrome warranting emergency surgery consisting of a laminectomy for debridement/decompression followed by long-term antibiotic treatment., Conclusion: Epidural empyema is a major potential complication of lumbar ESI. Multiple markedly elevated inflammatory markers (WBC, ESR, CRP, and procalcitonin) and MRI evidence of an epidural empyema necessitates emergent surgical intervention to limit morbidity, neurological sequelae, and mortality., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)