OBJECTIVES Depression and anxiety are common in children with asthma, and asthma hospitalization is an underused opportunity to identify mental health concerns. We assessed depression and anxiety symptoms during asthma hospitalization and 1 to 2 months post discharge. METHODS This prospective cohort study included children aged 7 to 17 years who were hospitalized for asthma exacerbation. Participants completed the self-report PROMIS (Patient-Reported Outcomes Measurement Information System) depression and anxiety symptom scales (T score mean = 50, SD = 10) during hospitalization and 1 to 2 months after discharge. Higher scores indicate more symptoms and/or greater severity. We compared patients’ scores during hospitalization and at follow-up using paired t tests and examined individual patients’ depression and anxiety symptom trajectories using a Sankey diagram. RESULTS Among 96 participants who completed the study, 53% had elevated symptoms of depression, anxiety, or both either during hospitalization or after discharge. During hospitalization, 38% had elevated depression symptoms and 45% had elevated anxiety symptoms. At postdischarge follow-up, 18% had elevated depression symptoms and 20% had elevated anxiety symptoms. We observed all possible symptom trajectories: symptoms during hospitalization that persisted (especially if both depression and anxiety symptoms were present), symptoms that resolved, and symptoms that were present at follow-up only. CONCLUSIONS Just more than half of youth hospitalized for asthma exacerbation experienced depression and/or anxiety symptoms during hospitalization or at follow-up. Patients who had both depression and anxiety symptoms during hospitalization were the most likely to have persistent symptoms at follow-up. Screening at both time points may be useful to identify mental health symptoms.