Background: The aim of the study was to assess the influence of a single haemodialysis (HD) session on the retinal and optic nerve morphology in end-stage kidney disease (ESKD) patients. Methods: It is a prospective study including only the right eye of 35 chronic kidney disease (CKD) patients subjected to HD. Each patient underwent a full eye examination 30 min before HD (8 a.m.) and 15 min after HD. Optical coherence tomography (OCT) was used to assess the peripapillary retinal nerve fibre layer (pRNFL) thickness, macular nerve fibre layer (mRNFL) thickness, ganglion cell layer with inner plexiform layer thickness (GCL+), GCL++ (mRNFL and GCL+) thickness, total retinal thickness (RT) and total macular volume (TMV). The correlation was tested between such systemic parameters changes as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), body weight, plasma osmolarity and ocular perfusion pressure (OPP) and ultrafiltration volume with total RT and pRNFL thickness changes during HD. Results: In the results of a single HD session, we could observe a statistically significant increase in the total RT thickness (pre-HD 270.4 ± 19.94 μm, post-HD 272.14 ± 20.11 μm; p = 0.0014), TMV (pre-HD 7.48 ± 0.53 mm3, post-HD 7.52 ± 0.55 mm3; p = 0.0006), total pRNFL thickness (pre-HD 97.46 ± 15.71 μm, post-HD 100.23 ± 14.7 μm; p = 0.0039), total GCL+ thickness (pre-HD 70.11 ± 9.24 μm, post-HD 70.6 ± 9.7 μm; p = 0.0044), and GCL++ thickness (pre-HD 97.46 ± 12.56 μm, post-HD 97.9 ± 12.94 μm; p = 0.0081). We observed a significant correlation between the change in total RT and DBP change, as well as between body weight change and the change in total pRNFL thickness. There was also a correlation between total pRNFL thickness change and the presence of diabetes mellitus. Conclusion: Even a single HD session affects the retinal and pRNFL thickness, which should be taken into account when interpreting the OCT results in patients subjected to HD. The impact of changes after a single HD session on selected parameters requires further assessment in subsequent studies, including long-term observation.