OBJECTIVE: To examine the association of youth and caregiver HIV status, and other contextual and social regulation factors with youth mental health. METHOD: Data were from two longitudinal studies of urban youth perinatally infected, affected, and unaffected by HIV (N_=_545; 36% PHIV+ youth; 45.7% HIV+ caregivers). Youth mental health was measured using the Child Behavior Checklist, the Child Depression Inventory, and the State-Trait Anxiety Inventory for Children. RESULTS: HIV+ youth reported elevated scores on the CDI compared with HIV- youth. HIV+ caregivers reported fewer symptoms and were less likely to report scores in the clinical range for their children on the CBCL compared with HIV- caregivers. Caregiver mental health and parent-child communication and involvement were also associated with youth mental health. CONCLUSIONS: Youth who resided with HIV+ caregivers had better mental health. Future research needs to further explore the role of caregiver HIV infection in youth mental health. Understanding and building upon strengths of HIV-affected families may be an effective focus of interventions for this population.