Non-invasive methods are necessary for the diagnostic and follow-up of metabolic dysfunction-associated steatohepatitis (MASH). This study aims to perform a proteomic analysis on serum and liver samples from morbid obese (MO) women to identify key mediators of MASH. HPLC-MS/MS proteomics was conducted on serum and liver samples from a cohort of 174 MO women classified by liver histology: 44 normal liver (NL), 66 simple steatosis (SS) and 64 MASH. Serum proteomics identified 257 proteins. The MASH individuals had 13 altered proteins, 11 upregulated and 2 downregulated. Altered proteins are primarily involved in molecular pathways of the initial triggering and complement cascade (50%). Liver proteomics identified 2081 proteins, with 72 upregulated and 84 downregulated in MASH. These proteins are mostly involved in molecular pathways of amino acid metabolism (31,25%), antimicrobial peptides (20%), fatty acid metabolism (17,5%). We identified 13 altered proteins in serum of MASH: increased levels of fructose-bisphosphate aldolase, clusterin, collectin-10 and -11, scavenger receptor cysteine-rich-M130, attractin, pigment epithelium-derived factor, vitronectin, complement factor-H, thrombospondin-4 and apolipoprotein-AIV and decreased levels of sex hormone-binding globulin and adiponectin. These proteins can be part of a panel of biomolecules for the diagnosis or follow-up of MASH.