Abstract: Evidence of the involvement of the cardiovascular system in patients with COVID-19 is increasing. The evaluation of the subclinical cardiac involvement is crucial for risk stratification at admission, and left ventricular global longitudinal strain (LVGLS) may be useful for this purpose. A total of 87 consecutive patients admitted to the COVID Center were enrolled from December 2020 to April 2021. A complete echocardiography examination was performed within 72 hours from admission. The main outcome was the need for mechanical ventilation by way of orotracheal intubation (OTI) and mortality, and the secondary outcome was the worsening of the respiratory function during hospitalization, interpreted as a decrease of the ratio between the partial pressure of oxygen and the fraction of inspired oxygen (P/F) <100. Of 87 patients, 14 had severe disease leading to OTI or death, whereas 24 had a P/F <100. LVGLS was significantly impaired in patients with severe disease. After adjustment for risk factors, by considering LVGLS as continuous variable, the latter remained significantly associated with severe acute respiratory distress syndrome (P/F <100) (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.18 to 1.88, p = 0.001) and OTI/death (HR 1.63, 95% CI 1.13 to 2.38, p = 0.012). When using an LVGLS cutoff of -16.1%, LVGLS ≥ -16.1% was independently associated with a higher risk of severe acute respiratory distress syndrome (HR 4.0, 95% CI 1.4 to 11.1, p= 0.008) and OTI/death (HR 7.3, 95% CI 1.6 to 34.1, p = 0.024). LVGLS can detect high-risk patients at the admission, which can help to guide in starting early treatment of the admitted patients.