Abstract Background Myocardial and vascular alterations among post-COVID-19 patients are observed. The coupling between arterial stiffness with left ventricular (LV) myocardial function (ventricular-arterial coupling, VAC) is an important determinant of cardiovascular performance and cardiac energetics. The aim of the study was to investigate the spectrum of cardiac and vascular abnormalities at mid-term follow-up in post-COVID-19 patients. Methods We enrolled 25 hospitalized patients for COVID-19, at one and six months after hospital discharge. The ratio (PWV/GLS) of carotid-femoral pulse wave velocity (cf-PWV), as a marker of arterial stiffness, to global longitudinal strain (LV-GLS), as a marker of left ventricular performance, was estimated as a marker of arterial elastance/left ventricular elastance index the long-term. The comparison was conducted with age and sex-matched non-COVID-19 controls. Results There was no difference in age (56.8±11.6 y vs. 57.4±9.5 y; p=0.85) and male sex (64% vs. 68%; P=0.76) between post-COVID-19 and control subjects respectively. At one-month follow-up, significant impairment was noted between post-COVID-19 and control subjects regarding: VAC (−0.71±0.24 m/s% vs. −0.44±0.11 m/sec%; p<0.001), LV-GLS (−17.9±3.1% vs. −21.9±2.7%; p<0.001), cf-PWV (12.3±3.5 m/s vs. 9.6±1.9; p<0.001). At six-month follow-up, an improvement was observed but there still was significant difference between post-COVID-19 and control subjects in: VAC (−0.62±0.19 m/sec% vs. −0.44±0.11 m/sec%; p<0.001), LV-GLS (−19.3±2.9% vs. −21.9±2.7%; p=0.001), cf-PWV (11.7±2.7 m/s vs. 9.6±1.9 m/s; p=0.001). Moreover, it was observed at 1-month: VAC adverse correlation with the levels of IL-6 (r=−0.54; p<0.001), CRP (−0.71; p=0.011) and at 6-months: IL-6 (r=−0.47; p=0.003), CRP (−0.56; p=0.007). Conclusion Ventricular-arterial coupling is impaired 6 months following COVID-19 highlighting the possible effects of SARS-CoV-2 infection in left ventricular mechanics and performance. Funding Acknowledgement Type of funding sources: None.