Background: The prevalences of asthma and obesity in children have increased significantly during the past 2 decades. The basis for the relationship between pediatric asthma and obesity is not well established. Objectives: To explore the association between obesity and asthma severity in children and adolescents and to test whether obesity-induced inflammation, as characterized by serum C-reactive protein (CRP), is associated with increased severity of asthma. Methods: Retrospective cohort analysis of interview, physical examination, and laboratory test data from participants younger than 20 years in 2 rounds of the National Health and Nutrition Examination Survey (2001-2002 and 2003-2004). We also performed generalized ordered logistic regression to evaluate the effect of body mass index (BMI) z score and CRP level on asthma severity, controlling for the impact of age, sex, race, income, insurance, and tobacco smoke exposure. Results: Of the 77 million individuals younger than 20 years represented by this weighted sample, 19% met the study-defined criteria for asthma; most cases were defined as mild (11%) or moderate (6%); 2% had severe asthma. In multivariable models, elevated BMI z scores (odds ratio, 1.12; 95% confidence interval, 1.05-1.21) were associated with worse asthma severity. Elevated CRP level was associated with obesity (P < .001) and asthma severity (odds ratio, 1.33; 95% confidence interval, 1.16 -1.52). Conclusions: Higher BMI z scores and elevated serum CRP levels are associated with increased asthma severity. These findings highlight the importance of controlling for inflammation when considering the role of obesity and provide support for the hypothesis that obesity-induced inflammation may contribute to greater asthma severity.