The objective of this study was to evaluate the effect of three varieties of cactus cladodes resistant to carmine cochineal on the animal performance and histology of the large intestine of sheep. Forty lambs (21.0 ± 2.0 kg body weight) were distributed in a completely randomized design, with four treatments and ten repetitions. The experimental treatments consisted of a control diet and three more diets in which part (750 g/kg) of the elephant grass hay, and all the corn were replaced by Miúda cactus cladodes, IPA-Sertânia cactus cladodes, or Orelha de Elefante Mexicana (O.E.M.) cactus cladodes. On the 60th day after the introduction of the tested diets, blood samples were collected to quantify serum magnesium (Mg2+) levels. After 63 days of experiment, the animals were slaughtered and fragments of the cecum and colon were collected for histopathological analysis. The inclusion of the Miúda and O.E.M. cactus cladodes in the diet caused inflammatory lesions in the cecum (100% of the animals) and in the colon (71.43% of the animals) of the sheep. The inflammation in the cecum caused by Miúda and O.E.M. cactus cladodes was considered accentuated (P = 0.009). Less voluntary water intake was observed for animals submitted to diets with cactus cladodes (P < 0.001), as well as higher water content in the feces (P < 0.001). The cactus cladodes, especially the Miúda and O.E.M. varieties, cause lesions in the tissue morphology of the cecum and colon of sheep, but improve productive performance.