Abstract Objective. Physical activity (PA) may reduce the risk of coronary heart disease (CHD) by inducing beneficial changes in several risk factors. We studied the associations between PA and a range of risk markers of CHD in young adults. Methods and results. We measured serum lipoproteins, oxidized LDL, adipokines, inflammatory markers, metabolic markers, and arginine metabolites in 2,268 individuals (age 24–39 y). Participants were asked frequency, duration, and intensity of PA in leisure time. In addition, commuting to work was assessed. In both sexes, PA was inversely associated with waist circumference (all P < 0.0001). After controlling for sex, age, and waist circumference, PA was directly associated with HDL-cholesterol and apolipoprotein A1, and inversely with heart rate, smoking, oxidized LDL, apolipoprotein B, insulin, glucose, C-reactive protein, leptin, L-arginine, and phospholipase A2 activity (all P < 0.05). Conclusion. These population-based data are consistent with the idea that the beneficial effects of PA on CHD risk are mediated by favorable influences on several risk factors, as judged by independent relations to markers of lipoprotein metabolism, glucose metabolism, and inflammation. These associations reflect beneficial effects on cardiovascular health in both sexes and may offer mechanistic insights for the inverse association between PA and CHD.