This study aimed to assess the effects of diets containing spineless cactus genotypes resistant to carmine cochineal insect (Dactylopius opuntiae) on the liver condition of sheep. Thirty-six non-castrated Santa Inês male sheep (six months of age and average initial body weight of 22.0 ± 2.9 kg) were assigned to a completely randomized design, with three treatments and 12 replicates. The animals were fed a diet with Tifton hay as exclusive roughage (control) and two more diets in which the hay was partially replaced by ‘Miúda’ or ‘Orelha de Elefante Mexicana’ (OEM.) spineless cactus. The animals were randomly slaughtered at 86 days after 16-h solid fast. The use of spineless cactus, regardless of genotype, increased the liver weight and caused inflammatory processes and necrosis on the liver parenchyma. Spineless cactus in diets for sheep confined for 86 days, despite causing liver tissue damage, such as inflammation and death process of hepatocytes, does not compromise weight gain.