Objective: To examine (1) racial/ethnic disparities in health-related quality of life (HRQOL), and overall health status among African-American, Hispanic, and white 5th graders in the general population and (2) the extent to which socioeconomic status (SES) and other family contextual variables mediate any disparities. Methods: A total of 4824 African-American, Hispanic, and white fifth-graders participating in a population-based, cross-sectional survey conducted in 3 U.S. metropolitan areas reported their own HRQOL by using the Pediatric Quality of Life Inventory Version 4.0 and supplemental personal and social well-being scales. Parents reported these children's overall health status. SES was indexed by parent education and household income. Other family contextual variables included family structure and degree to which English is spoken at home. Results: Marked racial/ethnic disparities were observed across all measures of HRQOL and health status, favoring white children and especially disfavoring Hispanic children. Most of these disparities were no longer significant after adjusting for SES and other family contextual differences that were observed among these racial/ethnic groups. Only disparities in parent-reported overall health status and self-reported global self-worth remained. Conclusions: Racial/ethnic disparities in children's health status are substantial but may be mediated by corresponding disparities in SES and other family contextual variables. Race/ethnicity and family context are related to one another and should be considered jointly in efforts to reduce health disparities in children. Copyright © 2012 by Academic Pediatric Association.