The characterization of differentially expressed proteins (control vs. CF, F508del heterozygous vs. F508del homozygous, PS vs. PI, normal/mild vs. moderate/severe lung function impairment) showcased nine CF diagnosis biomarkers (CUTA, ARG1, EZR, AGA, FLNA, MAN1A1, MIA3, LFNG, SIAE) and seven CF severity biomarkers (ARG1, GPT, MDH2, EML4 (F508del homozygous), MGAT1 (pancreatic insufficiency), TOLLIP, IGJ (lung function impairment)) candidates as well as potential markers of CFTR phenotypic rescue to be further investigated for clinical relevance. This evidence concerns the gene MDH2 and exocrine pancreatic insufficiency.