Childhood obesity is a predisposing factor for adult cardiovascular diseases. Human serum paraoxonase (PON1) may protect against atherosclerosis by hydrolyzing lipid peroxides in oxidized LDL. Alterations and potential correlations of PON1 activities, leptin and adiponectin levels in childhood obesity were studied. We measured PON1 paraoxonase and arylesterase activities, anthropometric parameters, leptin and adiponectin levels in 59 white, obese (obese group-OB: BMI corrected for age: 95.1 +/- 3.5 percentile, age: 11.9 +/- 1.6 y) and 51 normal-weight children (control group-C: BMI corrected for age: 64.1 +/- 8.4 percentile, age: 12.0 +/- 3.9 y). Obese children had significantly lower PON1 paraoxonase (OB: 84.80 (64.33/144.74) U/L versus. C: 99.42 (83.33/152.05) U/L; p < 0.05) and arylesterase activities (OB: 94.40 (82.20/108.70) U/L versus. C: 115.20 (93.70/126.00) U/L; p < 0.01), higher leptin (OB: 37.05 (24.33/53.87) ng/mL versus. C: 4.62 (2.52/17.6) ng/mL; p < 0.0001) and lower adiponectin levels (OB: 7.56 (5.69/12.06) microg/mL versus. C: 11.51 (8.84/14.49) microg/mL; p < 0.001) compared with the normal-weight group. PON1 arylesterase activity showed inverse univariate correlation with leptin (r = -0.29; p < 0.05) and positive correlation with adiponectin levels (r = 0.39; p < 0.01). In multiple regression analysis adiponectin was strongly associated with PON1 arylesterase activity in obese children (beta = 0.45, p < 0.02). Our results emphasize the importance of the investigated metabolic alterations which may have further effects on cardiovascular morbidity and mortality in later adulthood. Altered levels of leptin, adiponectin and PON1 activities may be useful markers beside the general risk factors in childhood obesity.