Beginning in March 2020, the COVID-19 pandemic and response, which included physical distancing and stay-at-home orders, disrupted daily life in the United States. Compared with the rate in 2019, a 31% increase in the proportion of mental health-related emergency department (ED) visits occurred among adolescents aged 12-17 years in 2020 (1). In June 2020, 25% of surveyed adults aged 18-24 years reported experiencing suicidal ideation related to the pandemic in the past 30 days (2). More recent patterns of ED visits for suspected suicide attempts among these age groups are unclear. Using data from the National Syndromic Surveillance Program (NSSP),* CDC examined trends in ED visits for suspected suicide attempts† during January 1, 2019-May 15, 2021, among persons aged 12-25 years, by sex, and at three distinct phases of the COVID-19 pandemic. Compared with the corresponding period in 2019, persons aged 12-25 years made fewer ED visits for suspected suicide attempts during March 29-April 25, 2020. However, by early May 2020, ED visit counts for suspected suicide attempts began increasing among adolescents aged 12-17 years, especially among girls. During July 26-August 22, 2020, the mean weekly number of ED visits for suspected suicide attempts among girls aged 12-17 years was 26.2% higher than during the same period a year earlier; during February 21-March 20, 2021, mean weekly ED visit counts for suspected suicide attempts were 50.6% higher among girls aged 12-17 years compared with the same period in 2019. Suicide prevention measures focused on young persons call for a comprehensive approach, that is adapted during times of infrastructure disruption, involving multisectoral partnerships (e.g., public health, mental health, schools, and families) and implementation of evidence-based strategies (3) that address the range of factors influencing suicide risk.