There is limited understanding of pain and its relationship to mental health in Latinos, and limited knowledge about the biobehavioral mechanisms that underlie pain–mental health interrelations. To address these gaps, the present investigation sought to address whether anxiety sensitivity explained relations between pain intensity and anxious arousal, depressive symptoms, social anxiety, and depressive and anxiety disorders among an economically disadvantaged Latino sample. Participants included 349 adult Latinos (88% women; Mage = 38.8) who attended a community-based primary health care. In the multiple mediation model, anxiety sensitivity physical concerns accounted for the association between pain intensity and anxious arousal symptoms, cognitive concerns accounted for the association between pain intensity and depressive symptoms, and social concerns accounted for the association between pain intensity and social anxiety symptoms. This is the first study to demonstrate the explanatory role of anxiety sensitivity in pain-affective associations among disadvantaged Latinos.