Dyslipidemia is a feature that is commonly observed in patients of β-thalassemia major. The role played by PCSK9 in the development of such observation had never been studied before. This study aims at investigating the status of PCSK9 and its possible role in the development of dyslipidemia in a group of β-thalassemia major patients from Jordan. A total of 60 β-thalassemia major patients and 40 healthy subjects were included in this study. Clinical and biochemical data were collected using standard techniques. PCSK9 enzyme concentration was determined using Enzyme-linked immunosorbent assay (ELISA). Ferritin concentration was assessed using Enzyme-Linked Immunofluorescent assay (ELIFA), while lipid profile was determined using chemistry autoanalyzer. Lipid parameters including total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were all significantly lower in patients than in controls (p < 0.05). As expected, concentrations of ferritin were significantly higher in patients than in controls (p < 0.001). PCSK9 concentrations (pg/mL) were significantly lower in patients than in healthy controls (2261 ± 552 vs 2356 ± 384; p < 0.05). The levels of PCSK9 in the patient group were not influenced by age or gender. Levels of PCSK9 correlated positively with lipid parameters except for HDL-cholesterol. Serum ferritin correlated negatively with PCSK9 (r = 0.274; p < 0.05), and with total cholesterol (r = 0.298, <0.05). The results of this study suggest that the altered lipid profile in thalassemia patients might be attributed in part, to the low levels of PCSK9. The low levels of PCSK9 are likely to be caused by hyperferritinemia that may directly influence lipid metabolism, or indirectly through altered levels of PCSK9.