Socioeconomic disadvantage contributes to health inequities, including chronic pain. Yet, research examining socioeconomic disadvantage and pain risk in Native Americans (NAs) is scant. This exploratory analysis assessed relationships between socioeconomic position (SEP), ethnicity, and neighborhood disadvantage on pronociceptive processes in 272 healthy, chronic pain-free NAs (n=139) and non-Hispanic Whites (NHWs; n=133) from the Oklahoma Study of Native American Pain Risk (OK-SNAP). Neighborhood disadvantage was quantified using the Area Deprivation Index (ADI). Regression models tested whether ADI predicted pain-promoting outcomes (i.e., peripheral fiber functionality, pain sensitivity, pain and nociceptive amplification, endogenous pain inhibition) above-and-beyond SEP and ethnicity. The Ethnicity x ADI interaction was also tested. Of the 11 outcomes tested, 9 were not statistically significant. Of the significant findings, neighborhood disadvantage predicted impaired inhibition of the nociceptive flexion reflex above-and-beyond SEP and ethnicity. Additionally, ethnicity moderated the relationship between ADI and warm detection threshold; disadvantage was associated with higher thresholds for NAs, but not for NHWs. Together, results suggest neighborhood disadvantage is associated with reduced C-fiber function and impaired spinal inhibition; thus, pointing to a role of neighborhood disadvantage in the relationship between the environment and pain inequities. PerspectiveThis study assessed neighborhood socioeconomic disadvantage and pronociceptive processes in chronic pain-free Native Americans (NAs) and non-Hispanic Whites (NHWs). Irrespective of ethnicity, greater neighborhood disadvantage predicted less descending inhibition of spinal nociception. Neighborhood disadvantage was associated with a marker of C-fiber impairment (higher warm detection threshold) in NAs only.