Background and aim. The nature of the association between obesity and poor prognosis of COVID-19 without the evaluation of other co-pathologies associated has not yet been clearly evaluated. The aim of the present pair-matched case–control study was to investigate the outcome of patients with SARS-CoV-2 infection in obese and non-obese patients matched considering gender, age, number of comorbidities, and Charlson Comorbidity Index. Methods. All the adults hospitalized for SARS-CoV-2 infection and with BMI ≥ 30 kg/m2were included (Cases). For each Case, two patients with BMI < 30 kg/m2pair matched for gender, age (±5 years), number of comorbidities (excluding obesity), and Charlson Comorbidity Index (±1) were enrolled (Controls). Results. Of the 1282 patients with SARS-CoV-2 infection followed during the study period, 141 patients with obesity and 282 patients without were enrolled in the case and control groups, respectively. Considering matching variables, there was no statistical difference between the two groups. Patients in the Control group developed more frequently a mild–moderate disease (67% vs. 46.1%, respectively), whereas obese patients were more prone to need intensive care treatment (41.8% vs. 26.6%, respectively;p= 0.001). Moreover, the prevalence of death during hospitalization was higher in the Case group than in the Control group (12.1% vs. 6.4%,p= 0.046). Discussion. We confirmed an association between obesity and severe outcome of patients with COVID-19, also considering other factors associated with a severe outcome of COVID-19. Thus, in the case of SARS-CoV-2 infection, the subjects with BMI ≥ 30 kg/m2should be evaluated for early antiviral treatment to avoid the development of a severe course.