Background and Objective: Beta-thalassemia major is an important health problem in Iran. A high rate of psychiatric disorders has been reported in patients with thalassemia in different surveys and may be one of the reasons that cause problems in the quality of their sleep. Although sleep quality is important for the health and quality of life (QOL) of these patients, a limited study in Iran on sleep quality and its relation to the mental health status of these patients has been conducted so far. Materials and Methods: A total of 101 patients with thalassemia were assessed. Data were collected via a demographic information checklist, the Pittsburgh Sleep Quality Index (PSQI), and the 28-item General Health Questionnaire (GHQ-28). Results: Participants in this study had an average age of 25.90 ± 5.63 years and 71 (70.30%) of them were women. Seventy-seven patients (76.2%) suffered from poor sleep quality while the mean and standard deviation (SD) of the patients' total general health score (31.66 ± 11.35) was good at the general health level. Among the demographic factors, there was a significant relationship between job and sleep quality. Sleep quality, subjective sleep quality, sleep delay, sleep duration, sleep disorders, use of sleeping pills, and daily functional disorders had a positive and significant relationship with general health. Conclusion: Thalassemia reduces the quality of sleep. There is a positive and significant association between sleep quality and general health, meaning that by improving sleep quality, patients have a greater chance of improving their general health.