A 29-year-old male presented at the ER with a red and painful left eye with sudden and progressive loss of vision within a week. His visual acuity was 1/60. Slit lamp investigation showed inflammatory cells throughout the anterior chamber and vitreous body, and a hyperaemic and swollen optic disc with retinal lesions, indicating a panuveitis combined with multifocal chorioretinitis. Due to the progressive nature, an infectious cause was suspected: positive syphilis serology and HIV serology confirmed this. The diagnosis of ocular syphilis was a first manifestation of a syphilis infection. Moreover, this was a warning sign for an associated HIV infection. Approximately 40% of all syphilis cases in the Netherlands are co-infected with HIV. Due to the high co-infection rate, HIV should always be considered when diagnosing ocular syphilis. The ocular syphilis was treated as a neurosyphilis with 18 million units of penicillin per day, and the patient's vision eventually returned to 0.4.