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Previous research suggests that heavy metals may be associated with increased susceptibility to Helicobacter pylori infection. This study investigated the effect of heavy metal exposure (Pb and Cd) on tooth loss and H. pylori infection in a Chinese rural population, who live near a mining and smelting area. Blood samples were collected from the study participants to estimate the lead (Pb) and cadmium (Cd) exposure levels. H. pylori infection was analyzed using the 14C-urea breath test, and the number of missing teeth (MT), filled teeth (FT), and missing or filled teeth (MFT) were counted by conducting a physical examination. Regression analysis was used to assess the difference between H. pylori-positive and -negative individuals in the MT, FT, and MFT groups, adjusting for confounders. The H. pylori infection prevalence was higher in individuals in the high Cd or high Pb groups than that in the low Cd or low Pb groups (p < 0.05). In addition, greater numbers of FT and MFT were observed in individuals in the high Pb group than those in the low Pb group (p < 0.05). We further found 8.7% (95% CI, 2.8−23.8%, p = 0.017) of the effect of the high BPb level on H. pylori infection risk could be statistically explained by FT using amediation analyses in adjusted models, and 6.8% (95% CI, 1.6−24.8%, p = 0.066) by MFT. Furthermore, FT and MFT were significantly associated with increased risk for H. pylori infection (odds ratio (OR) = 4.938, 95% confidence interval (CI): 1.125−21.671; OR = 3.602, 95% CI: 1.218−10.648, respectively). Pb and Cd exposure may be associated with tooth loss and increased susceptibility to H. pylori infection, and tooth loss may be an independent risk factor for H. pylori infection.