Introduction Poor weight gain is one of the most important mortality hazards in cystic fibrosis (CF) patients. The mechanisms that may hinder body weight regulation are not completely understood. Leptin and its role in fat mass could be related to control of weight gain in CF patients. As the previous data are conflicting, we aimed to investigate serum leptin level in Iranian CF children compared to a control group. Material and methods Forty-three CF patients aged from 3 to 120 months and 43 age-matched controls were enrolled. Patients were recruited from the outpatient clinic of the Children's Medical Center Hospital. Controls were visited in the general outpatient clinic for an annual check-up. Both groups were divided into three subgroups based on age: 3 to 12 months, 13 to 48 months, and 49 to 120 months. Body mass index (BMI) was calculated for all the participants. Serum leptin levels were measured applying a solid phase enzyme-linked immunosorbent assay (ELISA). Results Leptin levels and BMI values were significantly different between patients and controls (p = 0.02, p < 0.001, respectively) but only patients aged 13–48 months had significantly higher levels of leptin than age-matched controls (p = 0.016). Overall male patients’ mean leptin level was significantly higher than in female patients (p = 0.032) and male controls (p < 0.001). Conclusions Leptin level in our patients was significantly higher than controls. It seems that leptin levels during infancy are higher than in adult patients. Further studies are required on specific genotypes, gender and age to reveal the probable correlation with BMI and leptin levels in CF patients from different ethnic groups.