Abstract Maternal opioid addiction is a significant public health concern, impacting the health and well-being of both mothers and their developing child during pregnancy and the postpartum period. Crucially, factors shaping maternal opioid use trajectories during pregnancy and after birth are not well understood. Emerging research indicates that elevated levels of psychosocial stress during pregnancy and the first year postpartum may explain increased risk for opioid relapse, consistent with a larger body of research that has documented the role of stress in the initiation and maintenance of addiction generally, and an emerging body of work focusing on parenting stress and addiction specifically. In the current application, we will employ a short-term longitudinal design to probe the biobehavioral mechanisms of psychosocial and parenting stress in pregnant women receiving medication assisted treatment (MAT) for opioid use disorder and demographically-matched pregnant women not receiving MAT. In pregnancy we will measure psychosocial stress and maternal tolerance of infant distress alongside characterizing craving and withdrawal symptoms. After delivery, mothers will complete monthly batteries of assessments to further characterize psychosocial and parenting stress and addiction symptoms. Additionally, mothers will complete neuroimaging assessments at 1 and 4 months postpartum to identify neural mechanisms of responding to infant (and non-infant) distress cues. Our biobehavioral characterization of psychosocial and parenting stress will then be employed in the prediction of MAT adherence. Taken together, this R01 application serves to identify a novel biobehavioral phenotype of psychosocial and parenting stress present in pregnancy and the early postpartum period that may confer increased risk for opioid relapse.