Background: To investigate the association between levels of active transport and leisure-time physical activity (LTPA) with C-reactive protein, white blood cell count, body mass index, waist circumference, and lipids in a large representative sample of adults residing in the United States. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey. Adjusted multinomial logistic regressions were carried out to quantify associations between levels of self-reported active transport (or LTPA) and quintiles of anthropometric measures and serum markers. Results: A total of 3248 adults were included. For serum inflammatory biomarkers, the authors observed a lower likelihood of being in the top quintile groups of circulating C-reactive protein (adjusted odds ratio [aOR]: 0.60; 95% confidence interval [CI], 0.40–0.90) and white blood cell count (aOR: 0.65; 95% CI, 0.44–0.95) with engaging in low to medium levels of active transport but not with high levels of active transport. Higher levels of LTPA were associated with lower likelihood of having high levels of serum inflammatory biomarkers (aOR: 0.60; 95% CI, 0.42–0.86 in the top C-reactive protein group and aOR: 0.58; 95% CI, 0.39–0.87 in top white blood cell group). Conclusions: Promoting active transport and/or LTPA may be a beneficial strategy to improving some, but not all, cardiometabolic health outcomes.