Objective: To investigate the combined association of obesity, diabetes mellitus (DM), and cardiovascular disease (CVD) with severe COVID-19 outcomes in adult and elderly inpatients. Design: Cross-sectional study based on registry data from Brazil's influenza surveillance system. Setting: Public and private hospitals across Brazil. Participants: Eligible population included 21,942 inpatients aged 20 years or older with positive RT-PCR test for SARS-CoV-2 until Jun 9th, 2020. Main outcome measures: Severe COVID-19 outcomes were non-invasive and invasive mechanical ventilation use, ICU admission, and death. Multivariate analyses were conducted separately for adults (20-59 years) and elders (>=60 years) to test the combined association of obesity (without and with DM and/or CVD) and degrees of obesity with each outcome. Results: A sample of 8,848 adults and 12,925 elders were included. Among adults, obesity with DM and/or CVD showed higher prevalence of invasive (PR 3.76, 95%CI 2.82-5.01) and non-invasive mechanical ventilation use (2.06, 1.58-2.69), ICU admission (1.60, 1.40-1.83), and death (1.79, 1.45-2.21) compared with the group without obesity, DM, and CVD. In elders, obesity alone (without DM and CVD) had the highest prevalence of ICU admission (1.40, 1.07-1.82) and death (1.67, 1.00-2.80). In both age groups, obesity alone and combined with DM and/or CVD showed higher prevalence in all outcomes than DM and/or CVD. A dose-response association was observed between obesity and death in adults: class I 1.32 (1.05-1.66), class II 1.41 (1.06-1.87), and class III 1.77 (1.35-2.33). Conclusions: The combined association of obesity, diabetes, and/or CVD with severe COVID-19 outcomes may be stronger in adults than in elders. Obesity alone and combined with DM and/or CVD had more impact on the risk of COVID-19 severity than DM and/or CVD in both age groups. The study also supports an independent relationship of obesity with severe outcomes, including a dose-response association between degrees of obesity and death in adults. These findings suggest important implications for the clinical care of patients with obesity and severe COVID-19 and support the inclusion of people with obesity in the high-risk and vaccine priority groups for protection from SARS-CoV-2.