Limited knowledge exists on the prevalence of comorbidity among pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL). To determine the prevalence of comorbidities present within 3 months before diagnosis among pediatric ALL/LL patients, and to examine if the prevalence varies by age, biological sex at birth, and race/ethnicity. We analyzed data on patients diagnosed with ALL/LL at ≤21 years of age from 1/1/2005 to 6/30/2020 (n=5,455), using electronic health records data from the TriNetX Research Network Database. Comorbidities examined included pulmonary, cardiac, cerebrovascular, vascular, developmental, immune, metabolic, infectious, genitourinary, digestive, muscle and connective tissue, and central and peripheral nervous system conditions. Overall, the prevalence of comorbidity was 34.1% (n=1,904), with significant differences observed based on sex and race/ethnicity. Females had a higher prevalence at 36.6% compared to males at 33.6% (p=0.024). Similarly, Non-Hispanic White (NHW) patients had a higher prevalence of 37.5% compared to 33.1% in other racial/ethnic groups (p<
0.001). Analyses of specific comorbidities revealed notable differences in the prevalence of infectious diseases by biological sex at birth (female: 9.7%, male: 7.0%, p<
0.001) and digestive diseases by age at diagnosis (≤10 years: 13.8%, >
10 years: 10.4%, p<
0.001). Although the overall prevalence of comorbidity at diagnosis showed minor differences across groups, disparities exist for specific comorbidities with females and younger patients having a higher prevalence of infectious diseases and digestive tract diseases, respectively. Future studies are needed to evaluate if these differences contribute to the disparities in treatment outcomes.