Opioid misuse in the context of pain management exacts a significant public health burden. Past work has established linkages between negative mood (i.e., symptoms of anxiety and depression) and opioid misuse/dependence, yet the mechanisms underlying these associations have received little scientific investigation. Anxiety sensitivity (AS), the fear of the negative consequences of internal states, may be relevant to better understanding negative mood-opioid relations among adults with chronic pain. Simultaneous indirect effects of negative mood on opioid misuse and opioid dependence via lower-order factors of AS (physical, cognitive, and social concerns) were examined cross-sectionally in the present study. The study sample consisted of 428 adults (74.1% female, = 38.27 years,  = 11.06) who self-reported current moderate to severe chronic pain and opioid use for chronic pain. Results indicated that negative mood was (in part) indirectly related to opioid misuse (in part) via AS physical and cognitive concerns and was (in part) indirectly related to opioid dependence via AS cognitive concerns only. No significant indirect effects via social concerns were observed: Findings suggest the importance of further exploring the role of anxiety sensitivity cognitive and physical concerns in terms of opioid misuse and dependence among adults with chronic pain.