Abstract: Objective To investigate the association of selenium (Se) concentration in the whole blood from pregnant women with congenital heart disease (CHD) in the offspring. Methods This case-control study enrolled pregnant women whose fetus were diagnosed with CHD by fetal echocardiography as cases (n=120), while those mothers with fetus without detected abnormality as controls (n=108). Maternal peripheral venous blood from all studied pregnant women were extracted and stored at the time of enrollment. The Se concentration was determined, and natural logarithm converted to LnSe to decrease the dispersion of distribution. LnSe level was divided into low, medium and high levels. Univariable and multivariable non-conditioned logistic models were used to explore the association of LnSe level and fetus CHD. Results The proportion of maternal education lower than high school, history of adverse pregnancy and smoking was higher in cases and controls with statistical significance(all P<0.05). Non-conditioned univariable logistic models showed that the medium and high level LnSe were significantly associated with decreased odd ratios(OR) of CHD and subtypes, compared with low level of LnSe. Adjusting for the factors of maternal age, prepregnant-BMI, maternal smoking, gestational week of samples collection and intake of folic acid, multivariable logistic regression analysis demonstrated that the adjusted OR for the high level LnSe was 0.29(95% CI:0.14-0.61), 0.37 (95% CI:0.17-0.82), 0.22(95% CI:0.07-0.64) and 0.11(95% CI:0.03-0.44) in CHD, septal defects, conotrucal defects and right ventricular outflow obstruction defects. The protective effect was stronger in high level LnSe than in medium level LnSe. Conclusions The High concentration of selenium in maternal whole blood is associated with decreased CHD in offspring.