Objective: To investigate clinically significant change in the emotional condition of relatives of patients with severe traumatic brain injury during sub-acute rehabilitation. Methods: Participants were 62 pairs of relatives and patients. Relatives completed the anxiety and depression scales from the Symptom Checklist-90-R (SCL-90-R) when the patients were admitted to sub-acute rehabilitation and at discharge. Improvement in emotional condition was investigated using the following criteria: (i) statistically reliable improvement; and (ii) clinically significant change (CSC). Results: At admission, 53.2% and 58.1% of relatives had scores above cut-off values on the anxiety and depression scales, respectively. On the anxiety scale 69.7% of these experienced a reliable improvement according to the Reliable Change Index (RCI) and 45.5% also obtained CSC, as their end-point was below the cut-off value. On the depression scale the corresponding figures were 44.4% and 41.7%, respectively. When comparing relatives with and without CSC, we found that CSC in symptoms of anxiety was associated with significantly better functional improvement during rehabilitation and a shorter period of post-traumatic amnesia in the patients. Conclusion: Of the relatives who reported scores above cut-off values on the anxiety and depression scales at patient's admission, approximately 40% experienced CSC in anxiety and depression during the patient's rehabilitation. Relatives of patients experiencing improvement during inpatient rehabilitation are more likely to experience CSC in anxiety.