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Objectives: The study objectives were to compare psychosocial well-being in individuals with spinal cord injuries/disorders (SCI/D) and above-mean (“high”) versus below-mean (“low”) pain interference, and to determine whether psychosocial well-being was negatively associated with pain interference. Methods: Data were collected via a cross-sectional survey mailed in late 2014 to early 2015 to a national sample of veterans with SCI/D who received prior-year Veterans Affairs healthcare and assessed demographics, injury-related factors, select health conditions, pain interference, and psychosocial well-being. Bivariate comparisons and multivariate linear regressions identified factors related to higher pain interference. Results: Approximately 79% of the sample (n = 813) reported high pain interference. Veterans with high (vs. low) pain interference reported worse perceptions of all included psychosocial well-being measures. Regression results indicated that higher pain interference was associated with higher grief/loss (β = 0.38, P < .0001) and negative psychosocial illness impact (β = 0.39, P < .0001), and lower positive affect (β = −0.39, P < .0001), resilience (β = −0.31, P < .0001), and life satisfaction (β = −0.39, P < .0001). Conclusions: The pain experience is independently associated with poor psychosocial well-being among individuals with SCI/D. Efforts to decrease perceptions of pain interference and improve factors associated with psychosocial well-being may symbiotically improve outcomes in SCI/D cohorts. Such efforts may focus on effective pain management programs aligned with patients’ treatment preferences.