OBJECTIVE: This study examined associations between mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-with maternal distress and pregnancy outcomes. METHOD: Participants were drawn from two pregnancy studies, EPI (N=187, USA) and BABIP (N=198, Turkey). Plasma cf-mtDNA and GDF15 levels were quantified using qPCR and ELISA assays. RESULTS: Plasma cf-mtDNA levels did not significantly vary across pregnancy, while plasma GDF15 levels increased from early to late pregnancy and decreased postpartum. Late 2nd trimester plasma GDF15 was negatively correlated with pre-pregnancy BMI (p=0.035) and gestational age (p=0.0048) at birth. Early 2nd trimester maternal distress was associated with lower cf-mtDNA (p<
0.05) and a trend for lower GDF15. Higher pre-pregnancy BMI and late-pregnancy maternal distress were linked to smaller postpartum GDF15 declines in EPI (p<
0.05). CONCLUSION: This study reveals distinct plasma cf-mtDNA and GDF15 patterns during the perinatal period, linking mitochondrial markers to maternal distress and pregnancy outcomes.