Objective: To evaluate the relationship between systemic inflammation and pulmonary function in persons with chronic spinal cord injury (SCI). Design: Cross-sectional study. Setting: Veterans Affairs Medical Center. Participants: Fifty-nine men with chronic SCI participating in a prior epidemiologic study. Methods: Standardized assessment of pulmonary function and measurement of plasma C-reactive protein (CRP) and interleukin-6 (IL-6). Main Outcome Measurements: Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Results: Persons with the highest values of IL-6 had the lowest %-predicted FEV1 and FVC. There was a significant inverse linear trend between quartile of IL-6 and %-predicted FEV1 (P < .001) and FVC (P < .006), unadjusted and adjusted for SCI level and completeness of injury, obstructive lung disease history, smoking, and body mass index (P = .010-039). Although not as strong as for IL-6, there also were similar trends for %-predicted FEV1 and FVC with CRP. Conclusions: In chronic SCI, higher levels of IL-6 and CRP were associated with a lower FEV1 and FVC, independent of level and completeness of injury. These results suggest that the reduction of pulmonary function after SCI is related not only to neuromuscular impairment but also to factors that promote systemic inflammation.