American Indians and Alaska Natives (ANs) report among the lowest levels of physical activity in the USA, but there is very little systematic research examining the determinants of physical activity patterns in these populations. This study investigated the relationships between enculturation (or cultural traditionality), psychosocial stress, and physical activity in a community-based sample of Yup'ik women and men living in rural AN communities. Associations between these variables and several metabolic risk factors were also examined.A sample of 488 Yup'ik participants (284 women and 204 men) from six villages in the Yukon-Kuskokwim Delta region completed a wellness survey and an array of physiological assessments [e.g., body mass index (BMI), blood pressure]. A subset of 179 participants also completed a 3-day pedometer assessment of physical activity.Multivariate linear regression models indicated that participants who were more enculturated (i.e., living more of a traditional lifestyle) and who experienced lower levels of psychosocial stress were significantly more physically active. In turn, both lower levels of psychosocial stress and higher levels of physical activity were associated with lower BMI, lower percent body fat, and lower waist circumference.Findings underscore the importance of gaining a culturally specific understanding of physical activity patterns in indigenous groups in order to inform effective health promotion strategies.