Aortic valve disease has recently been shown to have sex-specific pathobiology, where female valves experience more fibrosis and less calcification than male valves despite similar levels of stenosis. To investigate whether these differences were mirrored in a mouse model, six-week old male and female Ldlr-/-;ApoB100/100 mice were fed high fat diet to induce valve disease. After four or eight months on diet, blood lipid and sex hormone levels were measured, valve function was assessed by echocardiography, and valve leaflet tissues were analyzed (immuno)histochemically and by polarized light microscopy to assess valve morphology and content. Males on high fat diet for eight months had more valvular dysfunction than females on diet, however male and female valve leaflets did not differ in size, thickness, or collagen content. However, polarized microscopy indicated more collagen remodelling in the base of the male leaflets compared to females, which could affect healthy valve mechanics. This study provides the first characterization of sex differences in a mouse model and sex-specific structural differences that relate to level of valve dysfunction.