Background: This study examined the role of sleep problems and sleep duration on stress-related HPA axis reactivity among urban, low income adolescents. A total of 84 adolescents (M age 13.36 years; 50% male; 95% African American) and their parents provided information on adolescents’ sleep problems and sleep quantity. Adolescents completed a standardized social stress test in the laboratory (the Trier Social Stress Test; TSST). Saliva samples collected before and after the TSST yielded measures of cortisol pre-test, 15 min post-test, and 55 min post-test, as well as overall cortisol secretion and its increase (AUCG and AUCI). More sleep problems and longer sleep duration predicted higher cortisol reactivity to the TSST, particularly among females. Self-reports of sleep were more consistently related to stress-related cortisol reactivity than parent reports. Sleep problems and longer sleep duration may place adolescents at risk for HPA axis hyper-reactivity to stress, contributing to academic, behavioral and health problems.