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Abstract. Introduction:. Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. Objective:. This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Methods:. Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Results:. Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. Conclusions:. These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.