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Orbital inflammatory syndrome (OIS) is a rare condition characterized by inflammation of orbital structures in the absence of underlying infection, neoplasm or endocrinopathy. The pathogenesis of OIS has not been fully described, but histopathology reveals diffuse lymphocytic infiltration of the involved structures. This disorder presents clinically as acute pain and swelling in the orbit and usually responds rapidly to high dose corticosteroids. This entity has been reported previously in seven patients with systemic lupus erythematosus (SLE). Herein, we describe a patient with SLE who developed OIS, review the previously reported cases that have occurred in association with SLE, and describe the diagnostic evaluation and therapy for OIS. This rare entity can pose both a diagnostic and therapeutic dilemma in SLE patients given immunoppressive therapy.