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Intrathecal drug delivery (IDD) has multiple indications, including chronic pain, spasticity, and spinal cord injury. Patients with an IDD device implanted who are undergoing decompressive spinal surgery may be at risk for intrathecal (IT) drug overdose in the perioperative setting. The present report describes a patient with an IDD device who underwent elective spinal surgery that was complicated by prolonged, severe alteration in mental status over several days, requiring discontinuation of his IT medications. The patient eventually returned to his neurological baseline by postoperative day 14. In the setting of severe spinal stenosis cranially in relation to an IDD device, consideration for weaning IT medications prior to elective surgery is recommended to avoid potential IT overdose. Patients undergoing weaning should be monitored for signs and symptoms of medication withdrawal.