Post-COVID-19 syndrome (PCS) is a multifactorial disorder comprising different subgroups. Our study aimed to investigate the longitudinal changes in retinal microcirculation in PCS patients. Eighty PCS patients were recruited at the Department of Ophthalmology at the Friedrich-Alexander University of Erlangen-Nürnberg. Retinal microcirculation was measured twice using optical coherence tomography angiography (OCT-A) within the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and peripapillary region. Vessel density (VD) was calculated using the Erlangen Angio Tool with an APSified and Bruch’s membrane opening-based analyses. The least-squares means (LS-Means) of VD were 30.4 (SE = 0.168) vs. 30.3 (SE = 0.166) (SVP), 22.4 (SE = 0.143) vs. 22.2 (SE = 0.141) (ICP), 23.9 (SE = 0.186) vs. 23.8 (SE = 0.185) (DCP), and 27.4 (SE = 0.226) vs. 27.0 (SE = 0.224) (peripapillary) in patients with PCS at visits 1 and 2, respectively. The study cohort showed physically stable PCS symptoms with PEM/fatigue and concentration disorders as major symptoms and only a slight, clinically irrelevant improvement of the Bell Score. The multivariate longitudinal model confirmed the clinical observations by showing that VD did not change significantly during follow-up (p = 0.46). Strong interdependencies between the macular layers (p < 0.001) were observed. The data of the present study suggests that while overall APSified macular VD and BMO-based APSified peripapillary VD were stable within a PCS cohort of physically stable PCS symptoms, individual patients may experience coordinated microvascular changes, particularly within the macular plexuses. Together, the results support a model of heterogeneous yet biologically consistent microvascular response in PCS pathophysiology.