Background Cystic fibrosis (CF) is an autosomal recessive disorder caused by a mutation in CF transmembrane conductance regulator gene (CFTR). Clinical manifestations of disease and their severity have considerable variations in patients having similar mutation in CFTR gene. This can be due to different polymorphisms, epigenetic changes and microRNAs (miRNAs) as gene modifiers. Considering the proven roles of miR-301b and miR-302b on infection and inflammation, expression of these miRNAs might change in CF patients. Materials and Methods: In this study, 30 CF patients (homozygous for ΔF508 mutation) and 30 healthy individuals were participated and their demographic data were recorded. The whole RNA was extracted from serum samples and cDNA was synthesized. Using Real-Time PCR, expression levels of miR-301b and miR-302b were measured between patient and normal groups. Patient classification was carried out based on Shwachman-Kulczycki score, and expression levels of these miRNAs were determined in these classifications. All statistical analyses were performed using IBM SPSS software V21. Results: Statistical analyses of qRT-PCR results showed a significant increase in serum levels of miR-301b and miR-302b expression (p-Values of 0.02 and 0.03; fold changes of 3.73 and 1.95, respectively) in CF patients compared to healthy controls. A significant increase (p<0.05) in miR-301b expression level was observed in severe, moderate and mild groups, while miR-302b expression level was increased in CF patients of severe and moderate groups according to Shwachman-Kulczycki score. Conclusion Expression levels of miR-301b and miR-302b are different based on clinical scoring system. This data suggests that expressions of these two miRNAs are influenced by infection and inflammation of CF patients. Further studies can lead to development of innovative treatment strategies.