BACKGROUND: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death. METHODS: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February-December 2020. Multivariate logistic regression identified the mortality risk factors. RESULTS: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07-14.76), obesity (adjOR 8.58, CI 3.30-22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06-94.22), heart disease (adjOR 17.68, 95% CI 3.80-82.18), cancer (adjOR 13.28, 95% CI 4.25-41.51) and male sex (adjOR 5.24, 95% CI 2.30-11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients. CONCLUSION: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals' death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.