Sympathetic ophthalmia (SO) is a rare, diffuse, bilateral, and granulomatous nonnecrotizing panuveitis that may follow intraocular penetrating trauma. Our aim is to report a rare case of SO following orbital exenteration. Orbital exenteration was performed on a 48-year-old african female due to conjunctival keratinizing squamous cell carcinoma with intraocular involvement of the left eye. Five days after the uneventful procedure, the patient presented signs and symptoms compatible with SO. Key differential diagnoses were excluded, and prompt and aggressive immunosuppression was started with a favourable but slow clinical response. This case highlights the fact that SO can also be induced by a neoplasm with intraocular invasion or by aggressive nonpenetrating surgery. While the underlying pathogenesis of SO is still not fully elucidated, we hereby contribute with a novel potential mechanism leading to its development.