Objective: To assess healthcare resource utilization (HRU) and costs in children of mothers with and without postpartum depression (PPD).Methods: Administrative claims data from the IBM Watson Health MarketScan Databases (2010-2016) were used. Women with live births (index date = delivery date) were identified and linked to their newborns. The mother-child pairs were divided into PPD and non-PPD exposure cohorts based on claims for depression, mood or adjustment disorders, or anxiety identified in the mother between 15 and 365 days after delivery. Mother-child pairs with PPD exposure were propensity score matched 1:3 to mother-child pairs without PPD exposure. Children were required to have 24 months of continuous health plan enrolment following delivery. Additional comparisons were performed between mother-child pairs with and without preterm delivery.Results: Overall, 33,314 mother-child pairs with PPD exposure were propensity score matched to 102,364 mother-child pairs without PPD exposure. During the 24-month follow-up period, HRU across most service categories was significantly higher among children in the PPD exposure cohort than non-PPD exposure cohort. Among outpatient services, the percentages of children with a physician specialist service (68% versus 64%), early-intervention screening (40% versus 37%), and an emergency room visit (48% versus 42%) were greater in children of mothers with PPD (all p < .001). Furthermore, children of mothers with PPD incurred 12% higher total healthcare costs in the first 24 months of life compared to children of mothers without PPD ($24,572 versus $21,946; p < .001). After excluding mothers with preterm delivery, the proportion of children with ER visits, physician specialist services, and outpatient pharmacy claims was significantly higher in the PPD exposure cohort than non-PPD exposure cohort (all p < .001).Conclusion: The results of this analysis suggest that HRU and costs over the first 24 months of life in children of mothers with PPD exceeded that of children of mothers without evidence of PPD.