BACKGROUND: Pediatric asthma is associated with increased health services utilization, missed school days, and diminished quality of life. Children with asthma also report more frequent depressive and anxiety symptoms than children without asthma, which may further worsen asthma outcomes. OBJECTIVE: The current study investigated the relationship between depressive and anxiety symptoms and 4 asthma outcomes (asthma control, asthma severity, lung function, and asthma-related quality of life) in children (N = 205) with moderate to severe persistent asthma. METHODS: The data were analyzed using a canonical correlation analysis, a multivariate framework that allows examination of all variables of interest in the same model. RESULTS: We found a statistically significant relationship between symptoms of depression and anxiety and asthma outcomes (1 - Λ = .372; P < .001). A large effect size suggests that 37.2% of variance is shared between depression and anxiety symptoms and 4 asthma outcomes (particularly asthma control and asthma-related quality of life) in the overall sample. Among girls (vs. boys), asthma control (measured by the Asthma Control Test) emerged as a stronger contributor to asthma outcomes compared with boys. CONCLUSIONS: These results suggest that psychiatric symptoms, especially anxiety, are associated with poor asthma-related quality of life, and more negative perception of asthma control in girls compared with boys (with no observed sex difference in physiological lung function). Clinicians should consider incorporating questions about psychiatric symptoms as part of routine asthma management, and focus patient education on unique differences in which boys and girls perceive their asthma symptoms.