Ceruloplasmin (CP) is an enzyme that has ferroxidase activity and is important in maintaining iron homeostasis and serving as a copper-transporter in the bloodstream. Beta-thalassemia major (BTM), a common hereditary disorder in Iraq, can affect CP activity in patients with iron overload resulting from frequent blood transfusions in order to sustain haemoglobin levels. The current study is a single-center observational research. CP activity was measured in 304 patients (120 females and 184 males). Anthropometric indices were recorded and the iron load status was determined by measuring serum ferritin. Ninety-two healthy individuals were also included as a control group. Our findings revealed no relationship between age, body mass index, or plasma ferritin and CP activity in BTM patients. No significant influence of sex on CP activity was observed. The outcomes provide insight into assumed pathways regulating CP, and add to the growing body of research on CP’s contribution to iron metabolism in BTM patients. To our knowledge, this work is the only study of its kind in Iraq, provides the groundwork for upcoming studies and potential therapeutic lines by generating insightful data on the multifaceted relationships between iron homeostasis, CP, and BTM.