In times of drought, the availability of feed is reduced, and the use of concentrate ingredients, such as wheat bran, becomes costly for animal production. Thus, the use of spineless cactus emerges as a potential solution to the shortage of feed and water during prolonged drought periods. The objective of this study was to evaluate the effects of replacing wheat bran with spineless cactus plus urea (0%, 25%, 50%, 75%, and 100%) in sugarcane-based diets for sheep on nutrient intake, feeding behaviour, nitrogen balance and microbial protein synthesis. Five male Santa Ines sheep with average initial bodyweight of 34.0 ± 3.6 kg were used in a 5 × 5 Latin square. The maximum intakes of dry matter (DM) (1414 g/day), organic matter (OM) (1281 g/day), crude protein (CP) (204 g/day), neutral detergent fibre corrected for ash and protein (NDFap) (425 g/day), and total digestible nutrients (TDN) (890 g/day) were estimated with replacement levels of 80.2%, 75.3%, 88.6%, 50.5%, and 79.3% respectively. Feeding behaviour was not altered by replacing wheat bran with spineless cactus plus urea. Nitrogen retention increased by 0.10 g/day, while plasmatic urea nitrogen increased by 0.20 mg/day for every 1% level of replacement. The maximum production of microbial nitrogen (15.9 g/day) and microbial protein synthesis (99.4 g/day) were estimated with replacement levels of 45.8 and 45.7%, respectively. It is concluded that up to 80% wheat bran could be replaced with spineless cactus plus urea in sugarcane-based diets for sheep.