Background Long-term use of prescription opioids for pain results in negative health outcomes. Overweight and pain are related, and adults with either condition commonly report poor sleep quality, high levels of depression, low levels of self-efficacy, and high pain interference and intensity. Insufficient research exists regarding how weight may influence pain outcomes in the context of common symptoms. Purpose To investigate how body mass index (BMI) influences relationships between health factors and pain outcomes among adults with pain prescribed opioids. Methods The sample included 226 adults. Linear regression models tested relationships among variables and outcomes of pain intensity and pain interference. Discussion BMI significantly strengthened relationships between health factors and pain interference but not pain intensity. Conclusion Adults with persistent pain suffer worsened pain interference in the context of increased weight status. Nurses should consider addressing BMI as part of a holistic pain management care plan.