Introduction: Placental blood biomarkers are dysregulated in adverse pregnancy outcomes (APO). While health behaviors are associated with APO risk, it is not well-characterized whether health behaviors impact placental blood biomarkers. Thus, we examined the associations between health behaviors and placental biomarkers of angiogenesis in mid-pregnancy. Hypothesis: Pregnant people engaging in healthier behaviors in the 1 st trimester would demonstrate more favorable 2 nd trimester concentrations of placental biomarkers. Methods: Data from 2,078 participants with available analytes from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be were included, representing an enriched sample of APO (preterm birth, preeclampsia/eclampsia, small-for-gestational age, or stillbirth; n=1,284) and 12% of those without these diagnoses (n=794). Health behaviors of physical activity, sleep, smoking, and diet assessed in the 1 st trimester were scored from 0-100 according to the Life’s Essential 8 algorithm; a higher score is more favorable. Biomarkers assayed included total endoglin, pregnancy-associated plasma protein A (PAPP-A), vascular endothelial growth factor, placental growth factor, and soluble FMS-like tyrosine 1. The association between health behaviors and each biomarker was examined using linear (continuous) or logistic (odds of concentration below multiple of the median [MoM] cut point) regression adjusted for demographics, BMI, resilience (Connor-Davidson Scale), and perceived discrimination (Krieger Racism Scale) using a backwards stepwise approach; analyses were repeated stratified by APO status. Bonferroni-corrected significance was p<0.001. Results: The overall APO rate in this enriched sample was 62%; this was significantly lower in those with ≥150 min/week compared with no physical activity (58% vs 66%, p=0.04). Lower (worse) smoking score was associated with lower (adverse) PAPP-A concentration in those who developed APO (p<0.001). Higher physical activity score (healthier) was associated with lower PAPP-A concentration (adverse) regardless of APO occurrence; for every 10-point higher physical activity score, odds of PAPP-A < 0.3 MoM increased 10% (OR 1.10; 95% CI 1.05, 1.16). No associations were observed between the other health behaviors and biomarkers. Conclusions: Higher levels of physical activity were associated with lower APO occurrence. In contrast, PAPP-A concentrations were lower in those with higher physical activity regardless of pregnancy outcome. Lower 2 nd trimester PAPP-A was observed in those with higher smoking exposure who developed APO. Our findings support prior work demonstrating lower risk of APO with more physical activity in pregnancy, but also indicate that PAPP-A concentrations may be sensitive to physical activity and smoking. Further work to elucidate the mechanisms of these associations is warranted.