Studies on dental caries suggest that in severe cases it may induce a systemic immune response. This occurs particularly when caries progresses into pulpal inflammation and results in abscess or fistula formation (AFF). We hypothesized that severe dental caries will affect the general health of children. The acute phase proteins alpha-1-acid glycoprotein (AGP), C-reactive protein (CRP) and the cytokine neopterin were chosen as parameters to monitor general health. Also, a polymorphism in the bacterial ligand CD14 (-260) was studied to investigate the relationship between genotype sensitivity for bacterial infections and AFF. In Suriname, children aged 6 years were recruited and enrolled into a dental care scheme, randomly assigned to 4 groups with different treatment strategies and monitored longitudinally. 348 children were included in the present study. Blood and saliva samples were taken at baseline and 1 year, and concentrations of serum AGP, CRP, neopterin, salivary Streptococcus mutans and CD14-260 C>T polymorphism were determined. There was no significant association between different treatment strategies and the serum parameters. Binary logistic regression analyses revealed a significant association between AFF as the outcome variable and the CD14 genotype and the concentrations of CRP and of neopterin as factors (p < 0.05). A significant negative association was found between the CD14-260 TT and AFF (p = 0.035, OR = 3.3) for the whole population. For children who had 4 or more carious lesions at baseline, the significance increased (p = 0.005, OR = 4.8), suggesting that the CD14-260 TT genotype was protective for AFF as a consequence of dental caries.