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Importance: The coronavirus disease 2019 (COVID-19) pandemic, associated mitigation measures, and social and economic impacts may affect mental health, suicidal behavior, substance use, and violence.Objective: To examine changes in US emergency department (ED) visits for mental health conditions (MHCs), suicide attempts (SAs), overdose (OD), and violence outcomes during the COVID-19 pandemic.Design, Setting, and Participants: This cross-sectional study used data from the Centers for Disease Control and Prevention's National Syndromic Surveillance Program to examine national changes in ED visits for MHCs, SAs, ODs, and violence from December 30, 2018, to October 10, 2020 (before and during the COVID-19 pandemic). The National Syndromic Surveillance Program captures approximately 70% of US ED visits from more than 3500 EDs that cover 48 states and Washington, DC.Main Outcomes and Measures: Outcome measures were MHCs, SAs, all drug ODs, opioid ODs, intimate partner violence (IPV), and suspected child abuse and neglect (SCAN) ED visit counts and rates. Weekly ED visit counts and rates were computed overall and stratified by sex.Results: From December 30, 2018, to October 10, 2020, a total of 187 508 065 total ED visits (53.6% female and 46.1% male) were captured; 6 018 318 included at least 1 study outcome (visits not mutually exclusive). Total ED visit volume decreased after COVID-19 mitigation measures were implemented in the US beginning on March 16, 2020. Weekly ED visit counts for all 6 outcomes decreased between March 8 and 28, 2020 (March 8: MHCs = 42 903, SAs = 5212, all ODs = 14 543, opioid ODs = 4752, IPV = 444, and SCAN = 1090; March 28: MHCs = 17 574, SAs = 4241, all ODs = 12 399, opioid ODs = 4306, IPV = 347, and SCAN = 487). Conversely, ED visit rates increased beginning the week of March 22 to 28, 2020. When the median ED visit counts between March 15 and October 10, 2020, were compared with the same period in 2019, the 2020 counts were significantly higher for SAs (n = 4940 vs 4656, P = .02), all ODs (n = 15 604 vs 13 371, P < .001), and opioid ODs (n = 5502 vs 4168, P < .001); counts were significantly lower for IPV ED visits (n = 442 vs 484, P < .001) and SCAN ED visits (n = 884 vs 1038, P < .001). Median rates during the same period were significantly higher in 2020 compared with 2019 for all outcomes except IPV.Conclusions and Relevance: These findings suggest that ED care seeking shifts during a pandemic, underscoring the need to integrate mental health, substance use, and violence screening and prevention services into response activities during public health crises. [ABSTRACT FROM AUTHOR]