We evaluated the effects of total water intake (TWI) deprivation and dietary supplementation with spineless cactus (Nopalea cochenillifera) cladodes on dry matter intake (DMI), average daily gain (ADG), feed conversion ratio and morphometric characteristics of rumen and intestinal tissues of Santa Inês sheep. Forty-two intact male Santa Inês sheep were used, with an average age of 100 ± 3 days and a body weight of 18.74 ± 2.05 kg. The animals were allocated to a completely randomised design in a 3 × 2 + 1 factorial arrangement with additional treatment of the control type, where (3) are cactus diets replacing Tifton-85 hay (30, 50 and 70% on dry matter (DM) basis) and (2) watering regimens (drinking water deprivation or ad libitum access to drinking water). The control treatment (1) contained 0% spineless cactus and had ad libitum access to drinking water). There was no interaction (P > 0.05) between spineless cactus inclusion and water deprivation on sheep performance. Water deprivation reduced (P < 0.001) TWI and increased (P < 0.001) the DMI/TWI ratio. It did not change slaughter body weight, total weight and ADG of sheep (P > 0.05). The spineless cactus inclusion quadratically increased (P ≤ 0.05) the DMI, slaughter body weight, ADG and feed efficiency. Contrary, TWI and DMI/TWI linearly decreased due to spineless cactus inclusion (P ≤ 0.05). Based on the means test, the DMI was higher at 30% inclusion level of cactus and decreased at 50 and 70%. There was no interaction (P > 0.05) between spineless cactus inclusion and drinking water deprivation for rumen papillae length, width and muscle thickness and intestinal mucosal height. The interaction between water and drinking water deprivation demonstrated that intestinal mucosal height (P ≤ 0.05) in the treatment with 50% inclusion was greater for the treatment with drinking water deprivation. A higher weight of the gastrointestinal tract was observed for the cactus substitution levels of 30 and 50%. The inclusion of 30% DM of spineless cactus replacing Tifton grass hay in sheep diet improved DMI, weight gain and feed conversion, regardless of the availability of drinking water. Drinking water deprivation in Santa Inês sheep receiving spineless cactus does not change the length and width of the ruminal papillae. However, sheep receiving spineless cactus increases the height of the intestinal papillae, irrespective of the inclusion level, because liquids facilitate the transportation of gastric contents, resulting in greater nutrient absorption.