Objective: This study sought to determine the association between periodontal disease in pregnancy and the delivery of low birth weight newborns in a rural population of South African women. Methods: This case-control study involved 348 new mothers. All subjects were recruited post-delivery from three public hospitals in the rural Eastern Cape of South Africa. The cases (n=119) were mothers who delivered through normal delivery and whose babies at the time of delivery weighed <2.5 kg. Age-matched controls (n=229) were mothers who delivered ≥2.5 kg babies. Potential risk factors for periodontal disease and low birth weight were collected by means of a structured questionnaire and maternity record review. Using the WHO's community periodontal index, a trained dental clinician blinded to participants' birth-outcomes recorded the periodontal health status of each participant (intraexaminer reliability; kappa = 0.95). Mothers who presented with a probing depth ≥4 mm on more than four index teeth without the presence of gingival overgrowth were deemed to present with periodontal disease. Data analysis included conditional logistic regression analysis. Results: Periodontal disease was diagnosed in 37.9%> (n=45) of the case group and 9.2°/o (n=21) of the control group. Low birth weight was also significantly more common among those who were unemployed, those who reported fewer than three antenatal visits and drinking on five or more days per week during pregnancy. After controlling for potential confounders, mothers presenting with a probing depth ≥ 4 mm on four teeth (OR = 4.12; 95°/o Cl = 1. 78 - 9.50) or more than four teeth (OR = 4.95; 95%> Cl: 1.52 - 15.81) were found to be significantly more likely to have low birth weight babies. Conclusions: The study findings suggest that there is a significant dose-dependent positive association between periodontal disease and low birth weight, independent of other risk factors measured in this study.