Background: This study aimed to compare flow-mediated dilation values between individuals with long COVID, individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and healthy age-matched controls to assess the potential implications for clinical management and long-term health outcomes. Methods: A case-case-control approach was employed, and flow-mediated dilation measurements were obtained from 51 participants (17 long COVID patients, 17 ME/CFS patients, and 17 healthy age-matched controls). Flow-mediated dilation values were analyzed using 1-way analysis of variance for between-group comparisons. Results: Results revealed significantly impaired endothelial function in both long COVID and ME/CFS groups compared with healthy age-matched controls as determined by maximum % brachial artery diameter post-occlusion compared with pre-occlusion resting diameter (6.99 ± 4.33% and 6.60 ± 3.48% vs 11.30 ± 4.44%, respectively, both P < .05). Notably, there was no difference in flow-mediated dilation between long COVID and ME/CFS groups (P = .949), despite significantly longer illness duration in the ME/CFS group (ME/CFS: 16 ± 11.15 years vs long COVID: 1.36 ± 0.51 years, P < .0001). Conclusion: The study demonstrates that both long COVID and ME/CFS patients exhibit similarly impaired endothelial function, indicating potential vascular involvement in the pathogenesis of these post-viral illnesses. The significant reduction in flow-mediated dilation values suggests an increased cardiovascular risk in these populations, warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.