A 45-year-old HIV-positive man receiving highly active antiretroviral therapy (HAART) presented with 6 weeks of right-sided headache and right eye pain. He had been diagnosed seropositive 2 years previously and screened negative for syphilis at that time. Examination demonstrated focal anterior scleritis with underlying retinitis and a mild vitritis. He was found to have positive syphilis serology and further investigations were consistent with neurosyphilis. Parenteral penicillin was commenced with prompt clinical response. This initial presentation of syphilis as acute scleritis emphasizes the need for thorough work-up of immunocompromised patients with inflammatory ocular disease.