Study design: Cross-sectional. Objectives: To determine the prevalence and severity of fatigue in persons with subacute spinal cord injury (SCI), assess whether demographic and lesion characteristics are related to fatigue and determine the relationship with physical fitness and physical behavior. Setting: Measurements were performed 2 months before discharge from inpatient rehabilitation. Methods: Thirty-six persons with subacute SCI, dependent on a manual wheelchair, mean age 43 +/- 15 and 83% men, completed the Fatigue Severity Scale (FSS). FSS scores 44 indicated fatigue. We recorded age and lesion characteristics, measured body mass index, measured peak power output and peak oxygen uptake during a maximal handcycling test and determined physical behavior using an accelerometer-based activity monitor. T-tests were used to test for differences in fatigue between subgroups based on age and lesion characteristics, and regression analyses to assess the relationship with physical fitness and physical behavior. Results: Mean FSS was 3.3 +/- 1.3. Fatigue, including severe fatigue, was prevalent in 31% (95% confidence interval: 16-46) of participants compared with 18% in the general population. Furthermore, mean fatigue was significantly higher in persons with incomplete compared with complete lesions (t=2.22, P=0.03). Mean scores between other subgroups did not differ significantly. Of the physical fitness and physical behavior measures, only peak oxygen uptake tended to be related to more fatigue (B=-1.47, P=0.05). Conclusion: Fatigue was prevalent and is of concern in persons with subacute SCI. Those with incomplete lesions seem to be at higher risk. Because fatigue is known to persist among persons with SCI, interventions to reduce fatigue seem necessary.