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Intro: Guillain-Barré syndrome (GBS) has been described to be associated with HIV infection. It is commonly present at seroconversion, wherein there is high viral load along with low CD4 count. It has also been reported rarely as immune reconstitution inflammatory syndrome (IRIS) associated with antiretroviral therapy (ART). Methods: A 21-year-old gentleman with vertically transmitted HIV was switched to second line anti-retroviral therapy 3 weeks prior to presentation (Baseline CD4: 8 cells/mm3, HIV-1 viral load: 820,265 copies/ml). He presented with 1 week history of progressive lower limbs weakness associated with reduced sensation, gradually ascended to involve upper limbs, with difficulty in swallowing. Findings: There was areflexia, loss of sensation in glove and stocking distribution, nasal speech and dysautonomia. Brain and spine magnetic resonance imaging showed no focal intracranial or intraspinal lesion. Cerebrospinal fluid examination (CSF) showed nil cell count with protein 0.83g/L, globulin positive, and a csf/serum glucose ratio of 0.46. Nerve conduction study showed prolonged F wave with sacral sparing and prolonged latency suggestive of demyelinating neuropathy. Patient diagnosed as GBS and received a 5-day course of intravenous immunoglobulin (IVIG). He had respiratory failure that required mechanical ventilation, which gradually improved and extubated. CSF was negative for HSV, VZV, CMV, Zika virus, cryptocococcus, mycobacterium and anti-GQ1b antibodies. Repeated HIV-1 viral load: 995 copies/ml. Discussion: The occurence of GBS is thought to be due to an autoimmune response against myelin sheath due to dysregulation triggered by HIV primary infection, which can also occur during IRIS. Risk factors for developing IRIS in our patient are HIV infection at younger age, rapid decline in HIV viral load, and low CD4 counts at baseline. Conclusion: It is crucial to differentiate GBS from other infectious causes of neuro-IRIS, thus appropriate treatment such as IVIG and plasma exchange can be administered early to prevent further disease progression and hasten recovery.