Background: The dysregulation of CC16 protein secreted by club cells (Clara cells) was reported in acute respiratory distress syndrome and Chronic obstructive pulmonary disease. We sought to investigate serum and urinary CC16 in asthmatic children in relation to asthma exacerbation and quiescence and correlate it to pulmonary function test results. Methods: This prospective controlled study was conducted in the Pediatric Allergy, Immunology and Rheumatology Unit, Children's Hospital, Ain Shams University on 40 atopic asthmatic patients, 6-12 years old, and 40 matched healthy controls, during the period from March 2020 to August 2021. Patients were enrolled consecutively during an asthma flare and were followed up to be re-evaluated at asthma quiescence. Patients were subjected to clinical assessment, skin prick testing to common aeroallergens, pulmonary function testing, and measurement of serum and urinary CC16 by ELISA during asthma exacerbation and quiescence. Results: Serum and urinary CC16 levels in patients during asthma exacerbation (median 243.5 and 137.5 ng/ml, respectively) and quiescence (median 112.5 and 55 ng/ml) were significantly higher than the levels in matched controls (median 15 and 13 ng/ml). Moreover, serum and urinary CC16 levels were higher during exacerbation than during quiescence (z=-5.214 and 4,941 respectively, p values < 0.001). Urinary CC16 showed a significant inverse correlation with best FVC% of predicted (r=-0.408, p= 0.009), but no significant correlation was found with age, BMI, age of onset of asthma, disease duration. Conclusion: Serum and urinary CC16 levels seem to be elevated in asthmatic children, especially during asthma exacerbation. Measurement of CC16 in urine might represent a non-invasive option that can replace blood sampling. Further wider-scale studies involving timely measurements of CC16 are needed to efficiently assess the role of CC16 as a biomarker of asthma exacerbation.