Background: Controversy exists about the mechanisms responsible for sex-based outcomes differences post-injury. X-chromosome-linked immune response pathway polymorphisms represent a potential mechanism resulting in sex-based outcomes differences post-injury. The prevalence of these variants is known to differ across race. We sought to characterize racial differences and the strength of any sex-based dimorphism post-injury. Study Design: A retrospective analysis was performed using data derived from the National Trauma Data Bank 7.1 (2002-2006). Blunt-injured adult (older than 15 years) patients, surviving >24 hours and with an Injury Severity Score >16 were analyzed (n = 244,371). Patients were stratified by race (Caucasian, black, Hispanic, Asian) and multivariable regression analysis was used to characterize the risk of mortality and the strength of protection associated with sex (female vs male). Results: When stratified by race, multivariable models demonstrated Caucasian females had an 8.5% lower adjusted risk of mortality (odds ratio [OR] = 0.91; 95% CI, 0.88-0.95; p < 0.001) relative to Caucasian males, with no significant association found for Hispanics or blacks. An exaggerated survival benefit was afforded to Asian females relative to Asian males, having a >40% lower adjusted risk of mortality (OR = 0.59; 95% CI, 0.44-78; p < 0.001). Asian males had a >75% higher adjusted risk of mortality relative to non-Asian males (OR = 1.77; 95% CI, 1.5-2.0; p < 0.001), and no significant difference in the mortality risk was found for Asian females relative to non-Asian females. Conclusions: These results suggest that Asian race is associated with sex-based outcomes differences that are exaggerated, resulting from worse outcomes for Asian males. These racial disparities suggest a negative male X-chromosome-linked effect as the mechanism responsible for these sex-based outcomes differences.