The opioid epidemic is a significant public health concern linked to chronic pain. Despite efforts to change opioid prescribing practices for chronic pain, opioid-involved overdoses remain at an all-time high. Research focused on identifying individual difference factors for problematic opioid misuse in the context of chronic pain have identified certain psychological variables that may confer heightened risk for opioid-related problems. Anxiety sensitivity, or fear of anxiety-related physical sensations, has been linked to opioid-related problems among adults with chronic pain. Yet, it is possible that these relations may not be distributed equally in society, and sex differences may be one avenue by which these relations differ. Therefore, the current study examined the moderating role of sex on the relation between anxiety sensitivity, current opioid misuse, and severity of opioid dependence among 428 adults (74.9% female, M = 38.28 years, SD = 11.06) with chronic pain. Results indicated that the relation between anxiety sensitivity and current opioid misuse (ΔR = 0.005, B = 0.12, SE = 0.06, p = 0.04), and opioid dependence (ΔR = 0.01, B = 0.04, SE = 0.02, p = 0.007) was stronger for males compared to females. These results suggest that anxiety sensitivity may be associated with opioid-related problems to a greater extent for males than females. Continued research is needed to examine how these sex differences may impact clinical treatment for opioid-related problems.