The main aim of this study was to determine the extent to which physical activity and adiposity are associated with blood cholesterol levels in male adolescents. Anthropometric and physical fitness values were measured in all children. Body mass index (BMI) and physical activity index (PAI) were used to split participants into active overweight (ACO) and non-active normal-weight (NAN) groups. The cutoffs for the ACO group were BMI > or = 22.6 kg/m2 and PAI > or = 3.5, respectively, whereas the corresponding cutoffs for the NAN groups were BMI < 20.0 kg/m2 and PAI < 2. A total of 65 children (29 in ACO group, 36 in NAN group) were selected according to the above criteria. ACO group showed significantly higher BMI and body fat as compared to their NAN counterparts (p < 0.05). Adolescents from ACO group attained superior scores for PAI and aerobic fitness (p < 0.05). Most blood lipid variables were significantly lower in ACO group as compared to NAN (p < 0.05) while HDL-cholesterol was higher in ACO group (p < 0.05). There was significant positive correlation between HDL-cholesterol and PAI in ACO group (r = 0.38; p < 0.05). The physical activity index explained the majority of variance in HDL-cholesterol for ACO group (beta = 0.513; p < 0.05). It seems that physical activity in adolescents is a more important factor in balancing blood lipid status than adiposity per se, particularly for HDL-cholesterol.