Background: An estimated 12,820 women in the United States will be diagnosed with CxCa in 2018, with 4,210 deaths from the disease. The economic burden of CxCa, both in terms of healthcare costs and lost productivity, has not been adequately studied. Methods: This was a mixed-methods study that evaluated the direct and indirect costs of CxCa using data from the Medical Expenditure Panel Survey (MEPS) for prevalent CxCa cases and the National Center for Health Statistics (NCHS) for deaths due to CxCa. Total healthcare costs and number of work days missed were compared between CxCa cases and controls in MEPS, using propensity scores calculated from baseline demographics and comorbidities. Missed work was converted to costs using the average hourly wage for women in 2015. Per-patient incremental healthcare and lost work productivity costs were then multiplied by the number of prevalent cases of CxCa in 2015 obtained from the Surveillance, Epidemiology, and End Results Program (SEER). NCHS data on the age-stratified number of CxCa deaths per year (1935–2015) and life expectancy data from the Social Security Administration were then used to calcluate the number of women who would be alive in 2015 if they had not died from CxCa and the lost earnings resulting from early mortality. The primary study outcome was the total direct and indirect cost of CxCa in 2015, calculated as the sum of the incremental direct healthcare costs, incremental lost productivity costs due to missed work, and lost productivity costs resulting from early death due to CxCa. Results: An estimated 257,524 women were alive with CxCa in 2015. Total healthcare costs were $4,221 higher, and an additional 0.37 work days were missed in women with CxCa compared to propensity-matched controls. Of the 488,475 women who died of CxCa prior to 2015, 108,832 would be alive in 2015 and 38,540 would be part of the workforce. Lost earnings in 2015 attributable to these deaths totaled $2.19 billion. The total economic burden of CxCa in the United States in 2015 was thus estimated at $3.3 billion (Table 1). Conclusions: CxCa was responsible for nearly $3.3 billion in direct and indirect costs in 2015. Early death among women with CxCa was the biggest driver of total economic burden.