This study characterized the prevalence of overweight and obesity and assessed their cardiometabolic comorbidities in the population aged 21–79 years living in the San Juan metropolitan area of Puerto Rico. We analyzed data from a household survey conducted in Puerto Rico between 2005 and 2007 that used a representative sample of 840 non-institutionalized adults living in the San Juan metropolitan area. Body mass index categories were classified as normal weight, overweight and obese. Poisson regression model with robust variance was used to estimate the prevalence ratio to assess the association of each cardiometabolic comorbidity (hypertension, dyslipidemia, diabetes, prediabetes, systemic inflammation, prothrombotic state, and coronary heart disease) with overweight and obesity. Age-standardized prevalence of overweight and obesity was 35.9 and 41.5 %, respectively, figures higher than the combined prevalence for the U.S. adult population (68.8 %) but similar to all mainland Hispanics (78.8 %). Men were more likely to be overweight than women (40.4 vs. 33.4 %), whereas more women than men were obese (43.7 vs. 37.6 %). Prevalence of all cardiometabolic comorbidities was significantly (p < 0.05) higher among overweight and obese adults than those of normal weight after adjusting for age, sex, years of education, smoking status, alcohol consumption and physical activity. A considerable proportion of adults in this population are overweight or obese. In view of the wide-ranging effects that overweight and obesity have on health, preventive actions to avert the rise of excess body weight as well as the design of lifestyle interventions are largely needed in this population.