Physical activity is considered beneficial and recommended for adults living with chronic pain. More information is needed to identify modifiable factors that affect their rates of physical activity. Two complementary, modifiable, adaptive responses to chronic pain that are related to levels of physical activity are psychological flexibility and self-regulatory efficacy (i.e., confidence) to overcome pain and related barriers to physical activity (SRE-pain). We wondered whether SRE-pain could be a potential mediator between psychological flexibility and physical activity. Thus, we prospectively examined whether SRE-pain mediated the psychological flexibility â€“ physical activity relationship among adults living with chronic pain (i.e., pain for > 6+ months). Participants (N = 193) completed online surveys at baseline, two weeks and four weeks (Time 1 through 3 respectively). Baron and Kenny's (1986) regression steps for testing mediation were conducted. The final hierarchical multiple regression revealed that the relationship between Time 1 psychological flexibility and Time 3 physical activity was reduced after controlling for Time 2 SRE-pain, F(2, 191) = 17.40, p < .001, accounting for 14% of the variance in Time 3 physical activity. A follow-up Sobel test confirmed that the reduction in that relation was statistically significant (Sobel z = 4.65, p < .001). Findings illustrated that SRE-pain could partially mediate the prospective relationship between psychological flexibility and later physical activity. The identification of a possible modifiable mechanism (mediator) that might allow adults living with chronic pain to be more flexible in their attempts to be active suggests future research should test this causal idea.