C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. We sought to determine (1) if 10 months of cardiovascular exercise training (Cardio) reduces CRP in a group of older adults, (2) if such a reduction is related to improvements in trunk fat, fitness, and/or psychosocial variables, and (3) if the effect of Cardio on CRP differs between men and women. Community-dwelling residents (n=127; 60-83 yrs) were randomized to a Flex group (n=61) where they participated in 2-75 min supervised sessions per wk during which they performed non-cardiovascular flexibility and balance exercises or a Cardio group (n=66) where they participated in three supervised sessions per wk during which they performed cardiovascular exercises for approximately 45-60 min at 60-70% maximal oxygen uptake. The main outcome measures were serum CRP, cardiovascular fitness, total and central adiposity, and self-reported psychosocial function. Cardio experienced a reduction in CRP (-0.5mg/L), as well as improvements in fitness (+7%) and total (-1.5%) and central (i.e., trunk) (-2.5%) adiposity. These relationships were not modified by sex. Regression analyses indicated that only the reduction in trunk fat was significantly related to the reduction in CRP. Ten months of cardiovascular exercise training reduced CRP in previously sedentary older adults and this effect was partially mediated by a reduction in trunk fat.