Objectives Some research has suggested a possible role for past infection in the development of preeclampsia. The objective of this study was to explore the role of Helicobacter pylori, cytomegalovirus, and Chlamydophila pneumoniae in the development of preeclampsia in a prospective pregnancy sample. Methods We conducted a nested case-control study in The Archive for Child Health (ARCH), a pregnancy cohort of 867 unselected women enrolled at the first prenatal visit with archived blood and urine in pregnancy. We matched 21 cases of preeclampsia to 52 unaffected controls on maternal age (+/- 4 years), race, parity, and gestational age at blood draw. Using conditional logistic regression, we examined the association between preeclampsia status and immunoglobulins G (IgG) tested by indirect ELISA to each of the three microorganisms, adjusting for potential confounders. Results No significant difference was found between cases and controls. The unadjusted odds ratio was 1.5 (95%CI: 0.2-9.1), 0.6 (95%CI: 0.2-1.9), and 1.9 (95%CI: 0.6-5.6) for H. pylori, cytomegalovirus and C. pneumoniae respectively. After controlling for confounders analysis found increased odds of H.pylori IgG (AOR: 1.9; 95% CI: 0.2-15.3) and C. pneumoniae IgG (AOR: 2.3; 95% CI: 0.6-9.2) for preeclampsia, albeit being not significant. Conversely, cytomegalovirus IgG had lower odds for preeclampsia (AOR: 0.4; 95% CI: 0.1-1.7). Conclusions Past infection with H. pylori, and C. pneumoniae in early pregnancy showed a higher risk of preeclampsia, but the findings failed to achieve statistical significance. Cytomegalovirus was not associated with preeclampsia in these data. These preliminary findings encourage future research in populations with high prevalence of these infections.