Background and objective: Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease among people in the USA and Europe with increased prevalence in Egypt. Pulmonary disease is the most important cause of morbidity and mortality in CF. The aim of our study is to detect most common organisms in Egyptian patients with CF and to correlate clinical status and severity of the disease with isolated organisms.Subjects and methods: The current study included 40 patients diagnosed as CF from the allergy and pulmonology unit aboreesh children’s hospital Cairo university. All patients are subjected to conventional sputum culture, PCR for fungi (suitable cultures), and PCR for Mycobacterium tuberculosis.Results: Out of 40, (24 patients) 60% have normal flora, (7) 17.5% have pseudomonas, (3) 7.5% have staph. aureus, (2) 5% have klebsiella ,(2) 5% have E. coli, (1) 2.5% has Acinetobacter, and (1) 2.5% has candida . PCR for fungi was done on suitable samples and detected that (24 patients) 72.7% have fungi in their sputum. PCR for TB was negative for all patients.Conclusion: In conclusion, our study confirms the presence of different pathogens infecting CF patients and the crucial role of sputum culture and PCR in early diagnosis allowing early and proper management. Further studies with a larger sample size are needed to clarify the organisms in Egyptian patients with CF and to correlate clinical status and severity of the disease with isolated organisms.