BACKGROUND Dexmedetomidine is a sedating agent approved for use in non-intubated patients and procedural sedation due to its efficacy in conscious sedation and minimal risks of respiratory depression. Previous reports proved the effectiveness of clonidine in treatment of withdrawal symptoms, but none have discussed cases with co-existing non-controlled psychiatric illness and prolonged duration of dexmedetomidine exposure. CASE REPORT We report a case of a 40-year-old woman diagnosed with viral meningitis. Due to her complicated psychiatric illness and viral meningitis, she developed severe agitation unresponsive to standard therapy. The patient had to be placed on dexmedetomidine, to which she developed dependence. There were several attempts to gradually withdraw dexmedetomidine but these were unsuccessful despite adding multiple antipsychotic medications. Withdrawal was manifested in multiple symptoms, including severe agitation, sweating, and tachycardia. Clonidine was used and was an effective treatment option to successfully withdraw the patient from dexmedetomidine. A smaller initial dose was used due to low baseline systolic blood pressure, which was successful. CONCLUSIONS This report proves that clonidine is an effective option for treatment of dexmedetomidine dependence compared to other antipsychotic agents. The present report is the first to discuss severe psychiatric illness and prolonged dexmedetomidine duration (>7 days) in a non-intubated patient. Dexmedetomidine withdrawal must be considered in the differential diagnosis of patients with psychiatric illness, which can be easily treated with clonidine.