The aim of the study was to investigate the association of leptin with hematological parameters in β-thalassemia patients in Greece. We measured plasma levels of soluble transferrin receptor (sTfR) and leptin by enzyme-linked immunosorbent assay (ELISA) in 40 β-thalassemia patients (21 transfusion dependent and 19 not transfused or sporadically transfused), in 20 β-thalassemia carriers, and in 30 healthy individuals (HI). The percentage of reticulocytes (RET) was measured by the NE 9500 Sysmex automated method. Body mass index (BMI) was calculated by dividing body weight (kg) by square height (m). Endocrine measurements including sex hormones were also determined. sTfR concentrations were significantly higher in both transfusion-dependent (females 10.5±2.9, males 9.1±3.1) and non-transfusion-dependent patients (females 15.8±5.4, males 19.8±13.7) as compared to carriers (females 3.1±2.5, males 3.8±1.8) and to HI (females 1.5±1.2, males 2.5±2.1). Leptin levels were lower both in female and in male transfusion-dependent patients (0.5±0.3 and 1.2±1, respectively) and in non-transfused males (1.9±2) compared to carriers (females 7.9±2.7, males13.1±9.1) and HI (females 14.6±6, males 7.5±3). There was a negative correlation between leptin and sTfR levels in transfused patients (R=–0.61, p<0.05). A stronger negative correlation (R=–0.7, p=0.006) was found in hypogonadic men and women with β-thalassemia. These findings enhance previous results indicating that leptin may play some role in hematopoiesis and could associate the pathophysiology of thalassemic patients with the triggering effect of leptin in reproductive ability.