Purpose To report the case of a patient with an inaugural severe bilateral vaso-occlusive retinopathy due to systemic lupus erythematosus. Method Clinical examination, fundus pictures and fluorescein angiography were performed. Results A 26-year-old, healthy, African man presented with a meningo-encephalitic syndrome and a severe bilateral visual impairment. The fundus examination revealed multiple retinal vascular occlusions, and a fluorescein angiography showed retinal and choroidal ischemia bilaterally. In addition, based on the neurologic disorders, a pleuritis, a renal disorder and a hematologic disorder, systemic lupus erythematosus, was diagnosed. Conclusions Severe vaso-occlusive retinopathy in a 26-year-old man resulting in a significant visual loss as the initial manifestation of systemic lupus erythematosus. Central nervous system involvement during lupus might be more frequent in patients when serious retinal changes occur.