Abstract Objective To test the hypothesis that the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is elevated in the circulation of patients with chronic spinal cord injury (SCI) relative to uninjured subjects, and secondarily to identify additional immune mediators that are elevated in subjects with chronic SCI. Design Prospective, observational pilot study. Setting Outpatient clinic of a department of physical medicine and rehabilitation and research institute in an academic medical center. Participants Individuals with chronic (>1y from initial injury) SCI (n=22) and age- and sex-matched uninjured subjects (n=19). Interventions Not applicable. Main Outcome Measures Plasma levels of MIF, as determined by a commercially available multiplex suspension immunoassay. The relationship between MIF levels and clinical/demographic variables was also examined. As a secondary outcome, we evaluated other cytokines, chemokines, and growth factors. Results Plasma MIF levels were significantly higher in subjects with chronic SCI than in control subjects ( P <.001). Elevated MIF levels were not correlated significantly with any one clinical or demographic characteristic. Subjects with SCI also exhibited significantly higher plasma levels of monokine induced by interferon-gamma/chemokine C-X-C motif ligand 9 ( P <.03), macrophage colony stimulating factor ( P <.035), interleukin-3 ( P <.044), and stem cell growth factor beta (SCGF-β) ( P <.016). Among subjects with SCI, the levels of SCGF-β increased with the time from initial injury. Conclusions These data confirm the hypothesis that MIF is elevated in subjects with chronic SCI and identify additional novel immune mediators that are also elevated in these subjects. This study suggests the importance of examining the potential functional roles of MIF and other immune factors in subjects with chronic SCI.