Objectives. To estimate the economic burden of untreated perinatal mood and anxiety disorders (PMADs) among 2017 births in the United States.Methods. We developed a mathematical model based on a cost-of-illness approach to estimate the impacts of exposure to untreated PMADs on mothers and children. Our model estimated the costs incurred by mothers and their babies born in 2017, projected from conception through the first 5 years of the birth cohort's lives. We determined model inputs from secondary data sources and a literature review.Results. We estimated PMADs to cost $14 billion for the 2017 birth cohort from conception to 5 years postpartum. The average cost per affected mother-child dyad was about $31 800. Mothers incurred 65% of the costs; children incurred 35%. The largest costs were attributable to reduced economic productivity among affected mothers, more preterm births, and increases in other maternal health expenditures.Conclusions. The US economic burden of PMADs is high. Efforts to lower the prevalence of untreated PMADs could lead to substantial economic savings for employers, insurers, the government, and society.