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We report two cases of macular infarction as a presenting sign of systemic lupus erythematosus (SLE).Ophthalmic examination and intravenous fluorescein angiography were supplemented by rheumatology consultations and imaging.Two patients presented with complaints of decreased vision in one or both eyes. Systemic manifestations included fever, rash, and arthralgias, while serologic tests revealed an elevated erythrocyte sedimentation rate and positive antinuclear antibody titers in both cases, confirming the diagnosis of SLE in each case. Ophthalmoscopic changes included cotton-wool spots, intraretinal hemorrhages, and retinal edema. Fluorescein angiography revealed macular infarction with extensive retinal capillary nonperfusion in both patients.Macular infarction is an uncommon but recognized complication of vasculitis associated with SLE. We report two additional cases of newly diagnosed SLE where vision loss secondary to macular infarction was the presenting sign of the disease. SLE should be considered in all patients who present with macular infarction. Visual prognosis is usually poor.