Youth in residential treatment settings often present with a complex combination of mental and physical health problems. Despite an emerging literature documenting significant associations between mental health and physical health, the relationship between these two areas of functioning has not been systematically examined in youth presenting to residential treatment. This study examines the association between youth psychopathology and physical health problems in a sample of 606 youth entering a large residential treatment program between 2003 and 2010. As a part of the intake process, youth psychopathology symptoms were assessed using the parent-report form of the Child Behavior Checklist, and youth physical health problems were assessed in a medical evaluation by a licensed child health professional. Results indicated that higher levels of youth psychopathology, particularly internalizing problems, were associated with greater risk for physical health problems and more prescription medications. Psychopathology comorbidity was also associated with physical health problems. These findings suggest an interplay between physical and mental health among youth entering residential treatment, highlighting the need for integrated assessment and intervention services that address psychological and medical needs within this population.