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PURPOSE To evaluate the relation between obstructive sleep apnea (OSA) and diabetic macular edema (DME) and the effect of OSA on refractory DME in patients with type 2 diabetes (T2DM). DESIGN Retrospective clinical cohort study. METHODS A population-based study was conducted at Chang Gung Memorial Hospital from March 1, 2009, to March 1, 2020. Among 14,152 patients who had undergone polysomnography (PSG) and whose data were registered on the sleep center's PSG database, 121 patients (242 eyes) with T2DM were enrolled according to the International Classification of Diseases, Ninth Revision (ICD-9) code for diabetic retinopathy (DR; 3620). Patients with a secondary etiology of macular edema and those lacking medical records were excluded. All patients with T2DM enrolled in our study received both optical coherence tomography and PSG. The prevalence of severe (apnea-hypopnea index [AHI] of ≥30) and nonsevere (AHI < 30) OSA was compared between patients with and without DME and refractory DME. RESULTS In total, 102 eyes (54 patients) were categorized into groups with (n = 40 eyes) or without (n = 62 eyes) DME. Severe OSA (odds ratio, 7.36; 95% CI, 1.32-40.96; P = .023) was significantly associated with DME. Refractory DME was significantly more frequent in patients with severe OSA (27%) than in those with nonsevere OSA (0%; P = .009). Cox proportional hazards regression analysis revealed that OSA (HR, 2.97; CI, 1.08-8.16; P = .034) independently increased the DME risk after adjustment for age, sex, glycohemoglobin level, hypertension, and hypercholesterolemia. CONCLUSIONS Severe OSA is a risk factor for DME and is associated with having refractory DME.