Objectives. To determine whether the COVID-19 pandemic affected e-cigarette use among young people in the United States.Methods. Data came from a weekly cross-sectional online survey of youths and young adults (aged 15-24 years). Logistic regression analyses measured odds of past-30-day e-cigarette use (n = 5752) following widespread stay-at-home directives (March 14-June 29, 2020), compared with the pre‒COVID-19 period (January 1-March 13, 2020). Logistic regression among a subsample of current e-cigarette users (n = 779) examined factors associated with reduced use following stay-at-home orders.Results. Odds of current e-cigarette use were significantly lower during the COVID-19 pandemic compared with the pre‒COVID-19 period among youths aged 15 to 17 years (odds ratio [OR] = 0.72; 95% confidence interval [CI] = 0.54, 0.96) and young adults aged 18 to 20 years (OR = 0.65; 95% CI = 0.52, 0.81). E-cigarette users with reduced access to retail environments had higher odds of reporting reduced e-cigarette use (OR = 1.51; 95% CI = 1.07, 2.14).Conclusions. COVID-19 stay-at-home directives present barriers to e-cigarette access and are associated with a decline in e-cigarette use among young people.Public Health Implications. Findings support the urgent implementation of interventions that reduce underage access to e-cigarettes to accelerate a downward trajectory of youth and young adult e-cigarette use.