INTRODUCTION: Acute zonal occult outer retinopathy (AZOOR) is a rare inflammatory retinal disease with rapid outer retinal function loss, photopsias, unremarkable fundus findings, and electroretinography abnormalities. AZOOR diagnosis can be challenging due to its overlap with other retinal conditions, such as acute idiopathic blind spot enlargement syndrome and autoimmune retinopathies (AIRs). Multimodal imaging, including fundus autofluorescence and optical coherence tomography, has improved detection, revealing progressive outer retinal damage. Although the etiology of AZOOR remains uncertain, autoimmune mechanisms and viral associations have been proposed. Recent studies have identified anti-retinal antibodies, complicating differentiation from other AIRs. CASE PRESENTATION: A 63-year-old male presented with photopsias, floaters, and worsening vision in his left eye. He had a prior diagnosis of AIR with serum antibodies against enolase, arrestin, and heat shock protein 27 (HSP27). Despite corticosteroid therapy, his visual acuity worsened from 20/20 to 20/60. Fundus examination showed subtle changes, and multimodal imaging revealed outer retinal damage consistent with AZOOR. He was started on mycophenolate mofetil, cyclosporine, and intravenous immunoglobulin. Over a year of follow-up, his vision improved to 20/25, and imaging showed stabilization of retinal damage. CONCLUSION: This case report highlights AZOOR can be associated with secondary np-AIR. Multimodal imaging, electrophysiologic testing of retina and retinal pigment epithelial, and anti-retinal antibody may be helpful for diagnosis of these patients. A combination of conventional immunomodulatory therapy and IVIg can help with controlling AZOOR and secondary np-AIR.