© 2016 The Authors. Published by Elsevier Inc. Background Depression has been associated with impaired nitric oxide (NO)-mediated vasodilation and vascular dysregulation (VD). Whether depression and NO levels will disturb retinal haemodynamics is not clear. Objectives and methods Associations between the retinal vasculature, diastolic ocular perfusion pressure (DOPP) as measure of hypoperfusion, NO metabolites (NOx) and depression symptoms were assessed. Chronic VD risk markers [depression symptoms (Patient Health Questionnaire/PHQ-9 ≥ 10) and 24 h pulse pressure] were determined in a bi-ethnic cohort (n = 313; 48.6 ± 9 years; 53.9% men). At 3 year follow-up, retinal vessel calibre and retinopathy signs were quantified from digital images. Salivary NOx was obtained pre- and post-flicker light-induced provocation (FLIP). DOPP was defined as diastolic blood pressure minus intraocular pressure. Results Chronic VD risk was evident in Blacks opposed to acute risk in Whites (P <0.05). At follow-up, retinopathy (Blacks 60.4%/Whites 39.6%), lower pre-FLIP (μM) and higher post-FLIP NOx (changes from baseline, %), arteriolar narrowing and wider venular calibre values were evident in Blacks compared to Whites, independent of confounders. A wider venular calibre, an index of stroke risk, was associated with chronic depression symptoms [cut point 248 MU: Area under the curve 0.61 (95% CI: 0.51, 0.72); 71% sensitivity; 55% specificity] as well as with hypoperfusion in the Blacks. In this group, arteriolar narrowing was associated with hypoperfusion; and attenuated arteriolar dilation with increased post-FLIP NOx responses. Conclusions Chronic depression symptoms may alter NO regulation and facilitate VD. NO-mediated vasoconstriction presumably impeded perfusion, retinal haemodynamics and -remodelling; potentiating stroke risk in Blacks.