BACKGROUND Obesity became a major public health problem as a result of its increasing prevalence worldwide. Paraoxonase-1 (PON1) is an esterase able to protect membranes and lipoproteins from oxidative modifications. At the PON1 gene, several polymorphisms in the promoter and coding regions have been identified. The aims of this study were i) to assess PON1 L55M and Q192R polymorphisms as a risk factor for obesity in women; ii) to compare PON1 activity according to the expression of each allele in L55M and Q192R polymorphisms; iii) to compare PON1 activity between obese and normal-weight women. METHODS We studied 75 healthy (35.9 ± 8.2 years) and 81 obese women (34.3 ± 8.2 years). Inclusion criteria for obese subjects were body mass index ≥ 30  kg/m² and absence of inflammatory/neoplasic conditions or kidney/hepatic dysfunction. The two PON1 polymorphisms were assessed by real-time PCR with TaqMan probes. PON1 enzymatic activity was assessed by spectrophotometric methods, using paraoxon as a substrate. RESULTS No significant differences were found for PON1 activity between normal and obese women. Nevertheless, PON1 activity was greater (P < 0.01) for the RR genotype (in Q192R polymorphism) and for the LL genotype (in L55M polymorphism). The frequency of allele R of Q192R polymorphism was significantly higher in obese women (P < 0.05) and was associated with an increased risk of obesity (odds ratio = 2.0 - 95% confidence interval (1.04; 3.87)). CONCLUSIONS L55M and Q192R polymorphisms influence PON1 activity. The allele R of the Q192R polymorphism is associated with an increased risk for development of obesity among Portuguese Caucasian premenopausal women.