IMPORTANCEThe COVID-19 pandemic disproportionately affected mental health in socioeconomically disadvantaged children in the US. However, little is known about the relationship of preexisting and time-varying social determinants of health (SDoH) at individual and structural levels, vaccination eligibility/rates, and the racial and ethnic differences to trajectories of child mental health during the COVID-19 pandemic.OBJECTIVE To estimate the association of trajectories of child mental health to multilevel SDoH and vaccination eligibility/rates. DESIGN, SETTING, AND PARTICIPANTS This prospective longitudinal cohort study, conducted from May 16, 2020, to March 2, 2021, integrated structural-level, pandemic-related data with the Adolescent Brain Cognitive Development (ABCD) cohort data (release 4.0). The ABCD study recruited 11 878 children (baseline) and conducted 6 COVID-19 rapid response surveys across 21 US sites (in 17 states) from May 16, 2020, to March 2, 2021. EXPOSURES Preexisting individual (eg, household income) and structural (area deprivation) SDoH and time-varying individual (eg, food insecurity, unemployment) and structural (eg, social distancing, vaccination eligibility/rates) SDoH. MAIN OUTCOMES AND MEASURES Perceived Stress Scale, the National Institutes of Health-Toolbox emotion measures, and COVID-19-related worry. RESULTS The longitudinal sample included 8493 children (mean [SD] age, 9.93 [0.63] years; 5011 girls [47.89%]; 245 Asian [2.34%], 1213 Black [11.59%], 2029 Hispanic [19.39%], 5851 White [55.93%], and 1124 children of other/multiracial ethnicity [10.74%]). Trajectories of stress, sadness, and COVID-19-related worry decreased after adult vaccination rollout.Compared with younger children, boys, White children, or those living with married parents, those who reported greater perceived stress included older children aged 12 to 15 years (β = 0.26; 95% CI, 0.12-0.41; P < .001); girls (β = 0.75; 95% CI, 0.61-0.89; P < .001); Hispanic children (β = 0.24; 95% CI, 0.01-0.47; P = .04); children living with separated parents (β = 0.50; 95% CI, 0.03-0.96; P = .04); children experiencing disrupted medical health care access (β = 0.19; 95% CI, 0.01-0.36; P = .04); children living in economically deprived neighborhoods (β = 0.28; 95% CI, 0.05-0.51; P = .02); children living in areas with more full-time working-class adults who were unable to social distance (β = 1.35; 95% CI, 0.13-2.67; P = .04); and children living in states with fewer fully vaccinated adults (β = 0.59; 95% CI, 0.16-1.02; P = .007). COVID-19 pandemic-related worry was higher among Asian children (β = 0.22; 95% CI, 0.08-0.37; P = .003), Black children (β = 0.33; 95% CI, 0.22-0.43; P < .001), children of other/multiracial ethnicity (β = 0.17; 95% CI, 0.09-0.25; P < .001), and children with disrupted medical health care (β = 0.15; 95% CI, 0.09-0.21) and disrupted mental health treatment (β = 0.11; 95% CI, 0.06-0.16). Inability to afford food was associated with increased sadness (β = 1.50; 95% CI, 0.06-2.93; P = .04). States with later ...