OBJECTIVE: Stressors from the COVID-19 pandemic and limited availability of mental health care services have negatively impacted youth mental health in a significant way. In the first year of the pandemic, global prevalence of anxiety and depression increased by roughly 25% in pediatric populations. While the general trend is clear, this research aimed to explore the added mental health burden of acute COVID-19 on pediatric patients with chronic conditions and describe the differences in mental health outcomes between pediatric patients with 2 common chronic conditions (asthma and diabetes) to better understand specific factors that may increase susceptibility to mental health concerns. METHOD: Using the TriNetX database, data were extracted for all pediatric patients (aged 5-17 years) with a positive SARS-CoV-2 infection (COVID-19) within a 1-year time frame (April 7, 2021, to April 6, 2022). These patients were divided into 4 cohorts based on the presence of chronic conditions before COVID-19 infection: diabetes (n = 1,587), asthma (n = 13,217), diabetes plus asthma (n = 626), and neither diabetes nor asthma (n = 104,427). For all cohorts, patients with other chronic illness and previous mental health diagnoses were excluded using relevant ICD-10 codes. After matching for demographics, comorbid conditions, and body mass index, odds ratios (ORs) of the following outcomes were compared between cohorts after 6 months: new psychiatric diagnosis using relevant ICD-10 codes, hospitalization within 1 week, and mortality. RESULTS: After matching, there were statistically significant differences in outcomes between patients with chronic illness and healthy controls after 6 months. Compared with healthy controls, the asthma cohort OR of developing a new psychiatric diagnosis was 1.4 (95% CI 1.15-1.71, p < .001), and the diabetes cohort OR was 1.81 (95% CI 1.11-2.94, p = .015). The new psychiatric diagnosis OR of the asthma cohort compared with the diabetes cohort was 0.62 (95% CI 0.39-0.99, p = .045), suggesting that patients in the diabetes cohort were particularly susceptible to additional mental health diagnoses after an acute COVID-19 infection. CONCLUSION: Compared with healthy controls, pediatric patients with asthma and pediatric patients with diabetes experienced increased odds of developing a new psychiatric diagnosis after an acute COVID-19 infection.