Background: Adult cardiorespiratory fitness (CRF) is associated with lower risk of cardiovascular disease and mortality. However, there is scarce information in youth about the role of CRF in subclinical measures of CVD, such as endothelial function. In this study we tested associations of cardiometabolic factors (CMF) and biomarkers of endothelial function (e-selectin; PAI-1). Methods: We included 1,380 participants (699 girls and 681 boys) aged 8-16 years from SOL Youth. CRF was assessed by a step test and VO2 max was estimated. CMF included fasting glucose, lipids, blood pressure. Inflammatory markers included hs-CRP and adiponectin. Associations of CRF with e-selectin and PAI-1 were assessed with multiple linear regression models, adjusting for potential confounders: actigraphy derived physical activity (PA) and sedentary time (SED), adiposity, and socio-demographic factors. Odds ratios were derived for the association of CRF and having ≥3 CVD risk factors (RF)(defined by elevated age/sex appropriate BP, lipids, glucose, and obesity), adjusted for confounders. Analyses accounted for complex survey design. Results: Boys and US-born youth were more likely to have higher CRF. CRF was positively correlated with PA (r=.23, p<.0001) but inversely correlated with SED (r=-.10, p=.001), BMIz-score (r=-.37, p<.0001), waist circumference (WC)(r=-.38, p<.0001), and %body fat (r=-.43, p<.0001). In multivariate models adjusting for socio-demographic factors, PA and SED (model 1), CRF was strongly and inversely associated with markers of endothelial function, inflammation, and CMF, which were attenuated when adjusting for WC (model 2)(Table 1). The odds of having ≥3 CVD RF was significantly lower at highest quartiles of fitness (ORs Q2=.47, Q3=.68, Q4=.35, p-trend=.001) after adjusting for confounders and WC. Conclusions: Among Latino youth, CRF appears to be a strong protective factor for endothelial dysfunction and CMF. Strategies to improve CRF may be a useful approach for improving cardiovascular health in youth.