Vitamin D is thought to modulate both innate and adaptive immune responses at the cellular level, but the relationship between vitamin D, infection, and inflammatory processes across pregnancy is unclear. The first objective of this study was to describe the prevalence of clinically diagnosed infections and to identify risk factors for infections. The second objective was to examine associations between vitamin D status, systemic inflammatory biomarkers, and infections across pregnancy. The third objective was to evaluate associations between vitamin D and placental antimicrobial peptide expression. To address these study aims, the prevalence of clinically-diagnosed maternal infections and placental inflammation was determined and potential risk factors were identified. We determined that African-American race, higher pre-pregnancy body-mass-index (BMI), younger age at diagnosis, and low intake of fat-soluble vitamins A and D were associated with greater infection prevalence. Using archived serum samples, we found positive associations between serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and the pro-inflammatory cytokines IL-6 and TNF-α during pregnancy, but inverse associations were observed between 1,25(OH)2D and both pro-inflammatory cytokines at delivery. In addition, lower serum 25-hydroxyvitamin D 25(OH)D status was associated with positive diagnosis of candida and bacterial vaginosis infections in these pregnant adolescents. In archived placental tissue samples, we found that the placental expression of vitamin D proteins (cubilin and CYP27B1) mediated the relationship between placental antimicrobial peptide expression and positive diagnosis of recto-vaginal group B streptococcus colonization in the mother. In summary, our results suggest that pregnant African American adolescents are at an increased risk for having sexually-transmitted and other vaginal infections during pregnancy, lower vitamin D status may increase risk of vaginal infections during pregnancy, and that vitamin D metabolites are associated with biomarkers of systemic inflammation and with the placental expression of antimicrobial peptides. Future research is needed to evaluate the potential for vitamin D supplementation to prevent and/or treat urogenital infections across gestation.