Introduction Health is determined by a complex interaction between individual characteristics, lifestyle and the physical, social and economic environment. Determinants affecting prenatal exposure to mercury (Hg) have influence on health of mother during pregnancy, newborns, and population at all. In our biomonitoring study, we tried to detect possible determinants of high Hg level in prenatal period. WHO Registration project 2016/623629-0 “Development of a Plan for Global Monitoring of Human Exposure to and Environmental Concentrations of Mercury”. Executing organizations: United Nations Environment Program, World Health Organization, WHO Regional Office for Europe, CNR-Institute of Atmospheric Pollution. Financing organizations: Global Environment Facility. Methods A human biomonitoring survey of 252 women in birth from five maternity hospitals of Republic of Karelia was carried out in 2016 using the WHO standard methodology (informed consent, woman's questionnaire, mercury (Hg) measurement in maternal hair and umbilical cord blood). All data were analyzed through appropriate descriptive statistics and statistical tests with level of significance: Xi-square, Mann–Whitney, Kruskal–Wallis. For detection of determinants affecting prenatal exposure to high Hg level the linear regression analysis was carried out. Results Prenatal exposure to Hg was characterized by high levels: the Geometric Mean (HgHair) was 0.534 μg/g (min 0.033 μg/g–max 8.000 μg/g), Hg concentrations exceeded referral level 1.0 μg/g in 23% of cases (58/252); the Geometric Mean (HgCordBlood) was 2.29 μg/L (min 0.13 μg/L–max 36.23 μg/L), Hg concentrations exceeded referral level 5.0 μg/L in 22.6% cases (57/252). The linear regression analysis defined positive and significant association with prenatal exposure to HgHair with womens’ age > 29.8 and negative and significant association with living in Karelia regions where Median Hg concentration lower than the general Median Hg concentration (B = 1.233, 95% CI: 0.989–1.477, P = 0.000; Y = 1.233 + 0.174X–0.506X; R2 = 0.177, P = 0.000). Also for HgHair level > 0.58 μg/g and HgHair level > 1.0 μg/g was defined one more positive and significant determinant: living in rural area (BHgHair>0.58 μg/g = 0.165, 95% CI: 0.014–0.316, P = 0.032; R2 = 0.136, P = 0.000; BHgHair>1.0 μg/g = 0.132; 95% CI: 0.006–0.258, P = 0.040; R2 = 0.148, P = 0.000). Among negative and significant determinants were find: broken thermometers in the nearest past (BHgHair>0.58 μg/g = −0.176, 95% CI: −0.350 to −0.002, P = 0.047; R2 = 0.136, P = 0.000), and rare consumption of local water fish (BHgHair>0.58 μg/g = −0.148, 95% CI: −0.279 to −0.017; P = 0.027; R2 = 0.136, P = 0.000). The linear regression analysis defined positive and significant associations with prenatal exposure to HgCordBlood with women's age > 29.8 and living in Medvezhyegorsk region where Median Hg concentration higher than the general Median Hg concentration (B = 2.826, 95% CI: 1.916–3.737; P = 0.000; Y = 2.826 + 0.995X + 2.422X; R2 = 0.147, P = 0.000). Also for HgCordBlood>15.0 μg/L high level was defined one more negative and significant determinant: rare consumption of local water fish (BHgCordBlood>15.0 μg/L = −0.045; 95% CI: −0.087 to −0.004, P = 0.032; R2 = 0.076, P = 0.003). Conclusions Detected determinants have significant effect on prenatal exposure to HgHair and HgCordBlood level in women of Republic of Karelia. Some detected negative and significant determinants (broken thermometers in the nearest past; rare consumption of local water fish) have needed to be more explored because of possible confounders. Finally, these findings will help to understand more clearly the situation with Hg exposure and to develop program for declining Hg exposure of population in Republic of Karelia.