Background: The impact of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) burden of disease in the United States is unknown. We sought to estimate and compare disability-adjusted life years (DALYs) lost because of OHCA during the COVID-19 pandemic to prepandemic values. Methods: DALY were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). Adult non-traumatic emergency medical services-treated OHCA from the Cardiac Arrest Registry to Enhance Survival database for 2016 to 2020 were used to estimate YLL. Cerebral performance category score disability weights were used to estimate YLD. The calculated DALY for the study population was extrapolated to a national level to estimate total US DALY. Data were reported as DALY total and rate. Data for 2020 (pandemic) were compared prepandemic years (2016–2019) via the chi-square test or t-test, as appropriate. Results: A total of 440,438 OHCA met study inclusion criteria. Total OHCA DALY in the United States increased from 4,468,155 (YLL = 4,463,988; YLD = 4167) in 2019 to 5,379,660 (YLL = 5,375,464; YLD = 4197) in 2020. The DALY rate increased from 1357 per 100,000 individuals in 2019 to 1630 per 100,000 individuals in 2020. Bystander cardiopulmonary resuscitation (CPR) rates did not significantly change (47.96% in 2016–2019 vs. 47.89% in 2020; p = 0.157). Conclusion: The overall burden of disease because of adult OHCA increased significantly during the COVID-19 pandemic. We observed no change in the willingness of layperson bystanders to perform CPR on a national level in the United States.