© 2017, The Society of Behavioral Medicine. Background: Racial differences in endogenous pain facilitatory processes have been previously reported. Evidence suggests that psychological and behavioral factors, including depressive symptoms and sleep, can alter endogenous pain facilitatory processes. Whether depressive symptoms and sleep might help explain racial differences in endogenous pain facilitatory processes has yet to be determined. Purpose: This observational, microlongitudinal study examined whether depressive symptoms and sleep were sequential mediators of racial differences in endogenous pain facilitatory processes. Methods: A total of 50 (26 African American and 24 non-Hispanic white) community-dwelling adults without chronic pain (mean 49.04 years; range 21–77) completed the Center for Epidemiological Studies Depression Scale prior to seven consecutive nights of sleep monitoring with actigraphy in the home environment. Participants subsequently returned to the laboratory for assessment of endogenous pain facilitation using a mechanical temporal summation protocol. Results: Findings revealed greater depressive symptoms, poorer sleep efficiency, and greater temporal summation of mechanical pain in African Americans compared to non-Hispanic whites. In a sequential mediation model, greater depressive symptoms predicted poorer sleep efficiency (t = −2.55, p = .014), and poorer sleep efficiency predicted enhanced temporal summation of mechanical pain (t = −4.11, p < .001), particularly for African Americans. Conclusions: This study underscores the importance of examining the contribution of psychological and behavioral factors when addressing racial differences in pain processing. Additionally, it lends support for the deleterious impact of depressive symptoms on sleep efficiency, suggesting that both sequentially mediate racial differences in endogenous pain facilitation.