Background/Objectives: Hemodialysis (HD) is the commonest life sustaining form of kidney replacement therapy in the world; however, this method of treatment have many adverse effects, and even a single HD session affects many organs, including the eyes. The aim of this study was to assess the effect of a single HD session on the ophthalmologic findings in patients with End-stage Renal Disease (ESRD). The second aim of the study was to examine the correlation of these changes with each other and between changes in systemic stressors related to the HD session. Methods: This was a single-center cross-sectional observational study conducted on 32 patients undergoing HD. Selected parameters of the anterior and posterior segment of the eye as well as systemic parameters were assessed before and after a single HD session. Results: Best corrected visual acuity (BCVA) improved, and lens thickness (LT), axial length (AXL), average macular thickness (MT), central MT and total vessel density (VD) of the deep capillary plexus DCP increased significantly after a single HD session. The Schirmer test results, tear break up time (TBUT), anterior chamber depth (ACD), central and average choroidal thickness (CT) decreased significantly after HD. Body weight loss was the only significant systemic change. Decrease in TBUT correlated positively with Schirmer’s test results decrease. Increase in CCT correlated positively with AXL increase. Decrease in central and average CT correlated positively with IOP decrease. Increase in central MT correlated positively with increase in average MT. Decrease in central CT correlated positively with average CT decrease. Change in VD of the SCP correlated positively with change in VD of DCP. Apart from the positive correlation between SBP change and Schirmer’s test results change, there were no correlations between systemic and ophthalmic parameters changes. Conclusions: Our study showed that HD affected the parameters of the anterior and posterior segments of the eye. Numerous correlations between these changes suggest that they are interrelated and represent the complex response of the eye to the HD process.