The aim of the study was two-fold; to determine the effect of a single step-aerobic exercise and an eight-week exercise program on muscle damage and to determine the effect of a single step-aerobic exercise and an eight-week exercise program on inflammation on sedentary females in low, moderate and high cardiovascular risk groups according to basal CRP classification. This study was performed at Nigde University, school of physical education and sports in Turkey. The subject group was composed of 18 middle-aged sedentary females who performed a step-aerobic exercise program 3 times per/week for eight-weeks. Cardiovascular risk classification was constructed according to basal CRP levels. Each subject underwent a 50-min step-aerobic exercise at the beginning and at the end of the program. CK and CRP were analyzed in blood sample. High risk group had higher body weight and body mass index (BMI). Subjects' CRP levels were significantly associated with their age, height, weight and BMI. Besides resulting in higher muscle damage in high risk group subjects, single exercise also caused significant differences in their CK and CRP responses. Additionally, applied eight-week exercise program resulted in a significant decrease in CRP in high risk group. Basal CRP levels were associated with physical characteristics and single exercise caused greater muscle damage in high cardiovascular risk group. CRP levels in high risk group decreased significantly after the exercise program.