The aim of this study was to compare the serum immunoglobulin A (IgA) and immunoglobulin G (IgG) levels and the presence of Treponema denticola in the root canals in a group of teeth with/without periapical lesion. A total of 66 children aged 8 to 13 years old were involved in this study. Five milliliters of blood samples were taken to detect the serum IgA and IgG levels. Sixty-six endodontic samplings were also obtained to determine the presence of T. denticola by polymerase chain reaction. The presence of T. denticola between the groups with/without periapical lesion was statistically significant (p = 0.026). A significant negative correlation was found between serum IgG and IgA levels and the presence of T. denticola (p = 0.023 and 0.038, respectively). This study may support the hypothesis that the presence of T. denticola in the root canals is mainly related to the periapical lesions, and the higher levels of serum IgG and IgA levels may protect against T. denticola.