<p>Individuals with persistent pain have disproportionately high cigarette smoking prevalence and poorer cessation outcomes. There has been a shift from examining single pain diagnoses to a focus on co-occurring pain disorders referred to as chronic overlapping pain conditions (COPCs). COPCs represent a cluster of 10 disorders (e.g., irritable bowel syndrome [IBS], fibromyalgia, chronic low back pain, chronic tension-type headache) characterized by central sensitization. Yet, the relevance of COPC burden on smoking-related processes and internalizing psychopathology remains unexplored. The purpose of the present study is to improve understanding of whether the total number of COPCs is associated with smoking-related processes, including cigarette dependence severity, perceived barriers for cessation, and severity of problems when trying to quit, as well as anxiety and depression severity. Participants were 263 adults (52.1% female; <i>M</i>_age = 44.1, <i>SD</i>_age = 12.71) recruited nationally with the COPC of IBS who smoked cigarettes daily and completed an online survey. Results indicated that the total number of COPCs was positively and statistically significantly associated with cigarette dependence severity, perceived barriers for cessation, and severity of problems when trying to quit, as well as depression symptom severity; a trending association with anxiety was also observed, though this did not survive Bonferroni correction. Findings suggest that greater COPC burden was associated with key smoking-related processes, thereby highlighting the potential clinical relevance of cumulative COPC comorbidity for cessation outcomes. The observed associations with depression and anxiety further underscore the role of internalizing symptoms as potential amplifiers of pain-smoking maintenance feedback loops.</p>