BACKGROUND: In HIV-infected patient who accompanied by syphilis often difficult to diagnose and difficult to treat. The aim is to diagnostics understanding and to optimise the management and response therapy in patients with neuroretinitis syphilis in HIV-infected patients. CASE PRESENTATION: A 53-years old, bisexual, male patient whose initial presentation was a blurry vision on the left eye. History of a painless genital lesion, HIV infection (+) on ARV therapy. The visual acuity of hand movement (HM), RAPD (+), with vitreous opacities and optic disc swelling. The OCT RNFL showed neural layer thickening in all areas. VEP showed increased P100 latency, normal head and orbital CT scan. High VDRL and TPHA titer. Lumbar puncture examination showed non-reactive VDRL. Treated with topical prednisolone eye drops, oral neurotropic vitamin, and intramuscular injection of Benzathine Penicillin G. Diagnosed with OS neuroretinitis et causa syphilis infection, HIV stage II on HAART. Follow up in 2 months, the visual acuity improved, and serology post-therapy VDRL was decreased. CONCLUSION: High accuracy is needed for screening signs and symptoms in syphilis patients because of the varied clinical manifestations. Ocular syphilis manifestation in HIV has a higher risk for neurologic complications and the risk of failing treatment with the standard regimen.