INTRODUCTION: Aortic valve sclerosis (AVSc) is an active pathological process driven by extracellular matrix remodeling, consistent with a potentially reversible early stage of aortic valve disease. METHODS: In this cross-sectional study of 168 participants (29, normal aortic valve [NAV]; 98, AVSc; 41, aortic stenosis [AS]), serum levels of matrix metalloproteinase (MMP)-1, -2, -3, and -9, tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor (TNF), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-β) were measured. Multivariable adjustments were performed. RESULTS: Compared with AS, AVSc was associated with higher circulating MMP-9 levels, with MMP-9 also increased relative to NAV. TIMP-1 concentrations were reduced in AVSc compared with both AS and NAV. TNF levels were higher in AVSc than in AS, while IL-6 and TGF-β did not differ among groups. Notably, MMP-9/TIMP-1 ratio was markedly increased in AVSc. DISCUSSION: Our findings suggest that AVSc may exhibit an active proteolytic and inflammatory profile amenable to targeted anti-inflammatory and anti-proteolytic interventions.