BACKGROUND: Patients with cystic fibrosis (CF) are highly susceptible to infection and colonization of pulmonary epithelia. Repeated and chronic infections may affect disease course and efficacy of host immune protection. Higher Interleukin (IL)-7 serum levels, indicating impaired T-cell response to IL-7, have been described for chronic viral and mycobacterial infections. METHODS: Time course measures of IL-7 serum concentrations in patients with CF (n = 164; n = 78 for the second time point) and healthy controls (n = 60) were done. CF patients were characterized for disease severity parameters as well as infection status and association with IL-7 serum levels was determined. RESULTS: CF patients had significantly higher IL-7 serum concentrations as compared to healthy controls (9.79 pg/ml, IQR 6.76-13.6 versus 4.55 pg/ml, IQR 2.76-9.51, p < .001). IL-7 serum levels were negatively correlated with individual CF patient's BMI (r = -0.19, p = .021) and a tendency of increased IL-7 levels in Staphylococcus aureus infected CF patients was found. Linear regression of multiple parameters revealed significant negative correlation of FEV1 with IL-7 serum concentrations in patients with CF (ß-coefficient: -0.04, 95% confidence interval [-0.08; -0.003], p = .034). Time course analyses after 1 year +/- 6 months showed increased IL-7 serum levels (time point 1:9.26 pg/ml, IQR 6.94-13.12 time point 2:10.86 pg/ml, IQR 9.14-14.76, p = .016) that correlated negatively with decreased FEV1 during CF disease course. CONCLUSIONS: High IL-7 serum levels were found in CF patients and correlated with impaired lung function during CF disease course. As a candidate biomarker of T-cell dysfunction, higher IL-7 serum level may also indicate worsened immune competence of patients with CF.