Objectives: Cardiorespiratory fitness (fitness) has been inversely associated with inflammation, but whether the association is attributed to fitness itself or lower levels of adiposity remains uncertain in young adults. The purpose of this study was to determine the association of fitness and adiposity with inflammation in young adults. Methods: A cross-sectional study was conducted with 88 participants aged 20–34 years. Fitness was assessed by a submaximal treadmill walking test. Adiposity was assessed by body mass index (BMI) and waist circumference (WC). Inflammation was measured by plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels using immunoassays. Biological data were log10 transformed. A separate multiple regression analysis was conducted with each inflammatory biomarker as a dependent variable. Covariates (sex, oral contraceptive use, and education level) were adjusted. Results: Fitness was inversely associated with log10 CRP after adjustment for covariates but not after adjusting for BMI or WC. Fitness was inversely associated with log10 IL-6 after adjustment for WC and covariates (β = −0.341, P =.049) but not after adjusting for BMI. Fitness × WC interaction (partial eta2 = 0.056, P =.033) indicated that high fitness was more strongly associated with low log10 IL-6 in young adults with high WC than those with low WC. Conclusions: Although adiposity has a stronger association than fitness with CRP and IL-6, higher levels of fitness could be essential for maintaining low levels of IL-6, especially in the presence of high levels of central adiposity.