OBJECTIVES: 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 with positive reverse transcription-PCR test for SARS-CoV-2 until 9 June 2020. MAIN OUTCOME MEASURES: Severe COVID-19 outcomes were non-invasive and invasive mechanical ventilation use, intensive care unit (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 8848 adults and 12 925 elders were included. Among adults, obesity with DM and/or CVD showed higher prevalence of invasive (prevalence ratio 3.76, 95% CI 2.82 to 5.01) and non-invasive mechanical ventilation use (2.06, 1.58 to 2.69), ICU admission (1.60, 1.40 to 1.83) and death (1.79, 1.45 to 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 to 1.82) and death (1.67, 1.00 to 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 to 1.66), class II 1.41 (1.06 to 1.87) and class III 1.77 (1.35 to 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.