Purpose <p>Spinal cord injury (SCI) is a complex medical condition and managing the multiple, co-occurring symptoms and functional and social limitations that follow SCI is a challenging task for clinical care providers. Understanding how the various post-SCI symptoms and limitations are interrelated or cluster together can inform patient care and improve clinical workflows. The purpose of this study was to determine the factor structure of the SCI-QOL measurement system and associated symptom clusters that affect health-related quality of life (HRQOL) in individuals with SCI.</p> Methods <p>Participants were individuals with SCI living in the community (&gt; 1 year after injury) recruited from 8 rehabilitation hospitals in the U.S. who completed 18 Spinal Cord Injury - Quality of Life (SCI-QOL) outcomes measures representing domains of physical, medical, social, and emotional health. Two dimension-reduction techniques, confirmatory factor analysis and multidimensional scaling, were used to analyze the data.</p> Results <p>Factor analysis results suggest 7 common factors underlying the measures: Physical Symptoms, Physical Function, Negative Affect, Positive Affect, Social Health, Independence, and Pain Interference. The psychosocial factors of Negative Affect, Positive Affect, and Social Health were highly interrelated. Large correlations were also observed between Physical Function and Independence, and between Physical and Social Health. All other interrelations were small to moderate. Results from the multidimensional scaling analysis were largely consistent with those from the factor analysis.</p> Conclusion <p>Study results will help inform the development of composite scores and symptom profiles in SCI, which will help researchers and clinicians better understand and manage symptoms following SCI.</p>