Patients suffering from complete spinal cord injury (SCI) are the most likely candidates for the application of new interventions for neural repair and regeneration. It is assumed that some of these treatments will have their strongest impact at the segmental level. Therefore, it is important to evaluate the clinical relevance of potential changes at the segmental levels concerning both improvement and deterioration. Data of 98 motor complete SCI patients were derived from the European Multicenter Study of Human Spinal Cord Injury database. Six months after injury, the ASIA motor score and Spinal Cord Independence Measure (SCIM) were assessed as dependent variables (linear regression analysis) to disclose the difference between each segment. Separate analyses using linear regression for tetraplegic patients (n = 39) and paraplegic patients with thoracic lesions (n = 54) were performed to calculate the difference between each spinal segment. In tetraplegic patients, both the ASIA motor score and the SCIM revealed relevant differences per spinal segment (9 and 4 points, respectively) while in paraplegic patients there was no difference for the SCIM and the ASIA motor score between T2 and T8. We suggest that in complete tetraplegic patients, changes of even one spinal segment will either improve or degrade both motor function and independence. Segmental changes at the thoracic level are not assessable by the ASIA motor score and SCIM tests. Therefore, the assessment of efficacy and safety in thoracic patients by these two tests has limited value when applied to cervical SCI. These findings may be considered in clinical trials for the evaluation of beneficial effects and risk management when treating patients with spinal cord injury.