Background: Tuberculosis (TB) is one of the most challenging public health burdens in the world. Recent research demonstrated high prevalence of mental disorders in TB patients and their caregivers. The purpose of this study was to assess mental health of TB patients and their caregivers in Iran before and after a two-week inpatient treatment and to determine the prevalence of psychological problems in these groups. Materials and Methods: A standardized questionnaire (SCL-90) was used to assess psychological symptoms in 146 hospitalized TB patients and their caregivers (n=89). Furthermore, the scores of both target groups were compared with those of a group of healthy individuals (n=85). Results: The mean scores before the start of the initial treatment of the patients were significantly lower for paranoid ideation (P=0.038) and hostility (P= 0.046), and the scores of depression (P=0.046) and somatization (P=0.001) were significantly higher than those of the healthy individuals. The patients scored significantly higher than the caregivers on depression (0.047) and somatization (p < 0.001), whereas the caregivers scored higher than the healthy individuals on paranoid ideation (P= 0.044) and hostility (P= 0.034). Multiple linear regression showed that age, educational level and marital status were factors affecting the mental health of TB patients and their caregivers. The variance in psychological symptoms of the patients was between 10% (paranoid ideation) and 27% (hostility) of the variance in the symptoms of their caregivers. Conclusion: Tuberculosis control and treatment programs should not only address issues like continued respiratory symptoms, but should also focus on mental health in TB patients and their caregivers.