Thyroid dysfunction substantially affects the quality of life due to its association with various disorders in different organs. A low intake of selenium and zinc can predispose to thyroid alterations, resulting in hypothyroidism. A deficiency of selenium and zinc causes direct and indirect skin lesions, both by the action of free radicals on the skin and by thyroid dysfunction. The aim of this study was to describe natural cases of diffuse alopecia and thyroid abnormalities in sheep with selenium and zinc deficiency. Five adult sheep presented marked and diffuse alopecia, and the residual hairs were dry and brittle. The skin was thick and crusty, with marked peeling. The triiodothyronine (T3) and thyroxine (T4) serum concentrations were below reference values for the species. Zinc and Se concentrations were low in both the serum and liver. During necropsy, cachexia associated with serous fat atrophy was observed, and the thyroid glands showed marked atrophy. Microscopically, the thyroid presented multifocal to coalescent atrophy, with atrophied and dilated follicles, macrophage infiltration, and the presence of fibrous connective tissue. The skin revealed hyperkeratosis and edema. It is concluded that thyroid atrophy, alopecia, and hyperkeratosis are associated with low serum and liver concentrations of zinc and selenium in sheep.