Abstract Cystic fibrosis (CF) is a common genetic disease caused majorly by autosomal recessive mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. In newborn, the disease can be noticed because it appears with meconium ileus. In males, the disease causes CF diabetes mellitus (CFRD), infertility, Progressive Pulmonary disease, increased chloride, and pancreatic exocrine insufficiency. Delay and/or prevention of morbidity and/or mortality are direct and positive outcomes of newborn screening for remediable genetic conditions as it permits early identification and intervention. In the Kingdom of Saudi Arabia (KSA) and the Arabian Gulf region, cystic fibrosis (CF) is thought to be more common than previously reported. Currently, measurement of Immuno Reactive Trypsinogen (IRT) in dry blood spots (DBS) is the gold standard method for initial newborn screening for CF, followed by targeted CFTR mutation analysis. However, while IRT is a known sensitive marker for CF detection in newborns only, it is also known to be not specific to Cystic Fibrosis. As such, our study, uses high resolution untargeted mass spectrometry-based metabolomics and lipidomics profiling to identify more reliable, sensitive, and specific biomarker(s) for CF in young and adult patients with CF. The identified biomarkers will then be characterized using high-resolution tandem mass spectrometry. A prototype essay will then be developed towards the gold standard LC-MS/MS based routine newborn screening. The biomarker sensitivity, specificity, and predictability will be validated in serum and dried blood spots (DBS). This newly discovered biomarker(s) may serve as an alternative (more reliable) diagnostic biomarker with additional prognostic and therapeutic value in patients with CF.