Key Clinical MessageMedication‐induced mood disorders following epidural steroid injections are possible therefore should be disclosed to the patient.AbstractMedication‐induced mood disorders have been rarely reported following epidural steroid injections (ESI). This case series presents three patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) criteria for substance/medication‐induced mood disorder after an ESI. In considering a candidacy for ESI, the rare but significant, side effects of psychiatric side effects should be disclosed to patients.