Living with chronic pain has been identified as a significant risk factor for suicide. Qualitative and cross-sectional studies have reported an association between mental defeat and suicidal thoughts and behavior in patients with chronic pain. In this prospective cohort study, we hypothesized that higher levels of mental defeat would be associated with increased suicide risk at a 6-month follow-up. A total of 524 patients with chronic pain completed online questionnaires measuring variables related to suicide risk, mental defeat, sociodemographic, psychological, pain, activity, and health variables. At 6 months, 70.8% (n=371) of respondents completed the questionnaires again. Weighted univariate and multivariable regression models were run to predict suicide risk at 6 months. The clinical suicide risk cutoff was met by 38.55% of participants at baseline and 36.66% at 6 months. Multivariable modeling revealed that mental defeat, depression, perceived stress, head pain, and active smoking status significantly increased the odds of reporting higher suicide risk, while older age reduced the odds. Receiver operating characteristic (ROC) analysis showed that assessment of mental defeat, perceived stress, and depression is effective in discriminating between ‘low’ and ‘high’ suicide risk. Awareness of the prospective links from mental defeat, depression, perceived stress, head pain, and active smoking status to increased suicide risk in patients with chronic pain may offer a novel avenue for assessment and preventative intervention. PERSPECTIVE: Results from this prospective cohort study suggest that mental defeat is a significant predictor of increased suicide risk among patients with chronic pain, along with depression, perceived stress, head pain, and active smoking status. These findings offer a novel avenue for assessment and preventative intervention before risk escalates.