Background <p>We aim to examine whether a spectrum of retinal parameters, are associated with depression in individuals with type 2 diabetes.</p> Method <p>We performed a cross sectional study of elderly patients with type 2 diabetes. Depression was measured with the Self-rated Inventory of Depressive Symptomatology 30 questionnaire, with scores ≥ 18 indicating depression. We evaluated retinal oxygen saturation, and retinal microvascular structures in individuals with type 2 diabetes and whether these were associated with increased risk of depression. Structural retinal parameters were measured in fundus photographs, and OCT-angiography scans, whereas retinal oxygen saturation was assessed with Oxymap Model T1. Main outcome was risk of depression. Multivariable logistic regression was used to investigate the association between retinal parameters and depression.</p> Results <p>We included 134 individuals with type 2 diabetes, of whom 22% had depression. Median (with interquartile range) age and duration of diabetes were 72 (69-76) and 19 (13-23) years and 70.2% were male. Depression was associated with higher retinal arteriolar oxygen saturation in the lower temporal quadrant (OR 1.71 95% CI 1.07-2.75 per SD increase). We found no significant association with retinal vessel width, tortuosity, density, fractal dimension, area of foveal avascular zone or area of non-perfusion.</p> Conclusion <p>We found some retinal metabolic but not vascular structures to be associated with depression, which therefore only partly support the notion that vascular factors may play a role in the pathogenesis of depression.</p> Trial registration <p>The study was registered at <a href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</a> before initiation (NCT04610749).</p>