The burden of disease associated with being African-American in the US, and the contribution of socio-economic status (SES) to that burden have not been quantified. We derived burden of disease estimates for African-Americans and whites by age group, with and without adjustment for SES (income and education). We used (1) EQ-5D Index scores from the 2000 US Medical Expenditure Panel Survey to derive quality-adjusted life year (QALY) compatible estimates of health-related quality of life (HRQL); (2) 1990-1992 US National Health Interview Survey data linked to National Death Index data through 1995 to derive mortality risks; and (3) 2000 US mortality data from the National Center for Health Statistics to derive current mortality estimates for the US population. We found that relative to whites, African-Americans suffer 67,000 more deaths annually, resulting in 2.2 million years of life lost, and 1.1 million years after SES adjustment. Total QALYs lost (HRQL and mortality) dropped from 2.3 million to 902,000 after SES adjustment. SES differences between African-Americans and whites appear to explain all the HRQL disparity but only half the mortality disparity. Better understanding of the disparate effects of SES may inform interventions to address health disparities adversely affecting African-Americans.