Introduction: Thalassemia prevalence in Malaysia is highest in Sabah. This study was conducted to characterize the demographic and socioeconomic profile of transfusion-dependent β-thalassemia major patients in Sabah, to explore their parents’ background, and to identify factors associated with having more than one thalassemia major children in the family. Methods: This was a cross-sectional study conducted in Hospital Wanita dan Kanak-Kanak Sabah and Hospital Kota Belud Sabah between February 2018 and Jun 2019. A total of 108 patients attending Thalassemia Treatment Clinic at both centers were selected randomly for interview. Results: β-thalassemia major patients in this study were majority from the indigenous ethnic groups (Kadazan, Dusun, Murut, Rungus, Sungai). Parents of the thalassemia patients mostly had low education level and socioeconomic status. Thirty-seven percent of parents have more than one children with thalassemia major and a high proportion (41.7%) have intermarriages. Parents with a higher number of children in the family are associated with having more than one thalassemia major children (OR: 2.1, 95% CI: 1.5, 2.9, P-value = 1.3 x 10-5). Conclusions: A considerably high proportion of parents have more than one children with thalassemia major in this study. Knowledge and counselling are important to parents with low educational level and socioeconomic status to ensure their understanding of thalassemia risk and prevention.