BACKGROUND: Understanding the impact of psychosocial factors and pain management on cardiovascular disease (CVD) risk and life expectancy in patients with chronic kidney disease (CKD) is critical for developing targeted interventions. We aimed to assess the associations of social isolation, loneliness, and pain risk with incident CVD in patients with CKD and to evaluate the impact of these factors on the life expectancy of CKD patients. METHODS: This prospective cohort study comprised 334,381 CKD patients from the UK Biobank. Loneliness and social isolation were measured using two-item and three-item scales, respectively. The Risk of pain spreading score (ROPS) was determined by summing responses to six items based on mood, trauma, sleep, neuroticism, and anthropometric measurement. The Cox proportional hazards regression model was used to evaluate CVD risk by estimating hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: Higher levels of loneliness (HR CONCLUSIONS AND RELEVANCE: The study findings suggest that addressing social isolation and loneliness, along with effective pain management, is crucial for reducing the risk of CVD and improving life expectancy in patients with CKD.