Anxiety sensitivity (fear of potential negative consequences of anxiety-related symptoms/sensations) has been identified as a transdiagnostic factor in comorbid pain and nicotine dependence and evidence suggests that anxiety sensitivity may be indirectly associated with nicotine use via greater pain severity. Therefore, this study tested the hypothesis that anxiety sensitivity is associated with cigarette and e-cigarette use/co-use directly and indirectly via greater pain severity. Participants included 273 online survey respondents with chronic musculoskeletal pain (34% female; M = 32.9). Anxiety sensitivity was positively associated with cigarette smoking, e-cigarette use and cigarette/e-cigarette co-use (ps < .05). Furthermore, anxiety sensitivity was indirectly and positively associated with cigarette smoking, e-cigarette use and co-use via greater chronic pain severity. Pain severity may play an important role in associations between anxiety sensitivity and nicotine dependence and prospective research should examine temporal/causal effects of anxiety sensitivity in relation to pain severity and nicotine/tobacco use.