Importance: There is limited evidence on whether the quality of life and behavior of children with special educational needs (SEN) have improved or worsened since schools reopened after COVID-19-related school closures. Objective: To describe the changes in the mental well-being of children and adolescents with SEN during the initial 6 months of resuming in-person learning after COVID-19-related school closures. Design, Setting, and Participants: This repeated cross-sectional study reported data from surveys completed by parents and caregivers of children and adolescents aged 3 to 18 years with SEN studying at special schools in Hong Kong. The first cohort was obtained during COVID-19-related school closure in April 2020 (wave 1) and the second cohort was obtained 6 months after school resumption with data collection between July and October 2021 (wave 2). Data analysis occurred from January to June 2022. Exposure: Diagnosis of a disability or disorder that required school-based special educational programming. Main Outcomes and Measures: Children's emotional and behavioral difficulties (measured with the Strengths and Difficulties Questionnaire [SDQ]), quality of life (measured with the Pediatric Quality of Life Inventory [PedsQL]), lifestyle habits, parental stress, and parental well-being (measured with the PedsQL Family Impact Module) were assessed. Cross-sectional comparisons of well-being between the 2 waves were conducted using analysis of covariance, and multiple regression analysis was performed to identify factors associated with mental health outcomes in wave 2. Results: In wave 1, a total of 456 parents and caregivers of children with SEN (mean [SD] age, 7.44 [3.98] years; 315 boys [69.1%]; 141 girls [30.9%]) responded to the surveys. In wave 2, 519 parents and caregivers of children with SEN (mean [SD] age, 8.16 [4.47] years; 365 boys [70.3%]; 154 girls [29.7%]) responded. After school resumption, preschoolers aged 3 to 5 years with SEN had significantly fewer emotional difficulties (mean [SD] SDQ score, 3.26 [2.39] vs 2.68 [2.03]; standardized mean difference [SMD] = 0.26; 95% CI, 0.07-0.46; Bonferroni-corrected P = .04) and conduct difficulties (mean [SD] SDQ score, 2.88 [1.89] vs 2.41 [1.91]; SMD = 0.25; 95% CI, 0.05-0.44; Bonferroni-corrected P = .01), whereas adolescents had more conduct difficulties (mean [SD] SDQ score, 1.62 [1.50] vs 2.37 [3.02]; SMD = 0.41; 95% CI, 0.13-0.70; Bonferroni-corrected P = .049). The overall quality of life of school-aged children with SEN aged 6 to 11 years worsened after school resumption (mean [SD] PedsQL score, 67.52 [17.45] vs 60.57 [16.52]; SMD = 0.41; 95% CI, 0.19-0.62; Bonferroni-corrected P = .002). Conclusions and Relevance: The findings of this repeated cross-sectional study suggest that preschoolers with SEN had improved emotional and behavioral functioning when school resumed after COVID-19-related closures. School-aged children with SEN, adolescents with SEN, and children with intellectual disabilities were at risk of reduced quality of life, indicating that additional support should be offered to vulnerable groups as they return to schools.