Purpose: Retinal oxygen supply is a critical requirement in ocular function, and when inadequate can lead to retinopathy. Endothelial dysfunction is a leading pathophysiology in diabetes and cardiovascular disease and may be assessed by endothelial microparticles (EMPs). We hypothesised links between retinal vessel oxygenation and EMPs, expecting these indices to be more adverse in those with both DM and CVD. Methods: Plasma from 34 patients with diabetes mellitus alone (DM), 40 with cardiovascular disease (CVD) alone and 36 with DM plus CVD was probed for EMPs by flow cytometry, but also for vascular markers soluble E-selectin (sEsel) and von Willebrand factor (vWf) (both ELISA). Retinal vessel fractal dimension, lacunarity, calibres and oxygen saturation were assessed from monochromatic and dual wavelength imaging respectively, intra-ocular pressure by was measured by rebound tonometry (I-CARE). Results: There was no difference in oxygenation (arterial p = 0.725, venous p = 0.264, arterio-venous difference 0.375) between the groups, but there were differences in EMPs (p = 0.049), vWf (p = 0.004) and sEsel (p = 0.032). In the entire cohort, and in diabetes alone, EMPs correlated with venous oxygenation (r = 0.24, p = 0.009 and r = 0.43, p = 0.011 respectively), while in DM + CVD, sEsel correlated with venous oxygenation (r = 0.55, p = 0.002) and with the arterial-venous difference (r = −0.63, p = 0.001). In multivariate regression analysis of vascular markers against retinal oximetry indices in the entire group, EMPs were positively linked to venous oxygenation (p = 0.037). Conclusions: Despite differences in systemic markers of vascular function between DM, CVD and DM + CVD, there was no difference in arterial or venous retinal oxygenation, or their difference. However, EMPs were linked to venous oximetry, and may provide further insight into the mechanisms underlying diabetes and diabetic retinopathy.