To determine the prevalence of anxiety and depression and impact on asthma control in pediatric patients with severe asthma.Children aged ≥4 years who were referred to the Boston Children’s Hospital Severe Asthma Program by a pediatric pulmonologist, allergist, or intensivist after a life-threatening asthma exacerbation.This was a single-center prospective cohort study from March 2017 to December 2019. Asthma severity for each participant was defined on the basis of the National Heart, Lung, and Blood Institute (NHLBI) asthma medication steps. At each clinical encounter, children completed the Patient Health Questionnaire (PHQ-4) and the Asthma Control Test (ACT) or childhood ACT with parental assistance and had spirometry done to assess lung function, including forced expiratory volume in 1 second (FEV1) to forced vital capacity. The association of the longitudinal psychological assessments and pulmonary function measures were determined by using a linear mixed model (adjusted for sex, age, race, and NHLBI asthma medication step).Data were obtained for 93 clinical encounters from 43 patients. The mean age was 11.7 (+/− 4.2) years; 65% were male (n = 28 of 43); 49% were White (n = 22 of 43). The median NHLBI asthma medication step was 5.5 (interquartile range: 4.5–6.0). A total of 58% (n = 25 of 43) had at least 1 symptom of anxiety and depression, and 19% (n = 8 of 43) had a PHQ-4 score >2, indicating at least mild impairment. Bivariate analyses after adjusting for age, sex, race, and medication step revealed a significant difference in mean ACT scores (7 points lower) for girls with a PHQ-4 score >2 versus that of those with a score ≤2 (95% confidence interval [CI]: −10.88 to −3.12; P = .01); this effect was not seen in mean ACT scores for boys with PHQ-4 scores >2 versus that of those with scores ≤2. Compared with girls, boys with PHQ-4 scores >2 had a mean ACT score that was 4.18 points higher (95% CI: 0.63 to 7.73; P = .03). A PHQ-4 score >2 was significantly associated with percent FEV1 predicted but not with FEV1 to forced vital capacity (95% CI: −33.83 to 1.12; P = .06).Pediatric patients with severe asthma often have comorbid mental health impairment, which is associated with poor asthma-related quality of life. Girls with greater anxiety and depression perceived significantly worse asthma control. No difference in perceived asthma control was seen in boys, regardless of anxiety or depression level.Individuals with poorly controlled asthma can have psychological comorbidities including anxiety and depression, whereas, conversely, these factors can exacerbate asthma and negatively impact asthma control and severity. The perception of asthma control may impact self-care, asthma self-management, and inaccurate perception of symptoms, potentially resulting in higher rates of asthma-related health care use. Just as women often are more likely to report symptoms than men, the girls in this study had the higher level of mental health impairment and more negatively perceived asthma control. Although sex differences were observed in the association between psychological impairment and perceived asthma control, there was no association with objective spirometry results. Study limitations include the small sample size and use of PHQ-4, which is not a standard psychological screening tool. However, with these results, the authors highlight the potential impact of psychological symptoms in our clinical management of patients with asthma.