We evaluated the effect of the sugarcane replacement (Saccharum officinarum L.) by cactus cladodes (Nopalea cochenillifera Salm-Dyck) at different levels (0, 180, 360, 540 and 720 g kg-1 on a dry matter (DM) basis) in the diet of sheep on nutrient intake and digestibility, ingestive behaviour, microbial protein synthesis, nitrogen and water balance, dry matter and fibre dynamics and ruminal parameters in sheep. Five castrated male crossbred sheep, with an initial average body weight (BW) of 63.38 ± 7.70 kg, were allocated in a 5 × 5 Latin square design. The intakes of DM (P < 0.001), crude protein (CP) (P = 0.009), neutral detergent fibre content adjusted for ash and nitrogen compounds (NDFcp) (P = 0.0016), non-fibre carbohydrates (NFC) (P < 0.001), indigestible NDF (iNDF) (P = 0.0018) and total digestible nutrients (TDN) (P < 0.001) showed a quadratic effect, and the replacement levels on DM did not affect nutrient digestibility. Rumination (P = 0.001) and idle (P = 0.001) times decreased with increasing levels of cactus cladodes. Plasma urea nitrogen (PUN) (P = 0.039) increased, and there was no effect on microbial nitrogen synthesis and microbial efficiency. The pools of DM (P = 0.037), NDF (P = 0.008) and indigestible NDF (iNDF) (P = 0.010) were reduced with increasing replacement levels. The DM ingestive (P = 0.005) and degradation (P = 0.005) rates increased, and the passage rate (P = 0.049) showed a quadratic response, with a maximum value of 0.035 h-1 estimated for 44% replacement. Intake (P = 0.004), degradation (P = 0.006) and passage (P = 0.016) rates of NDF, as well as the iNDF passage rate (P = 0.014), increased. The ruminal pH (P = 0.012) reduced with increasing replacement levels. Ruminal ammonia nitrogen (NH3-N) (P = 0.020) showed a quadratic response over time, presenting an estimated maximum value of 17.9 mg dL-1 at 0.68 h after feeding. Regarding volatile fatty acids, there was an increase for acetate (P < 0.001), whereas propionate was not influenced. The butyrate (P < 0.001) concentration demonstrated a quadratic effect, with a maximum value of 14.1 mmol L-1. Replacing up to 440 g kg-1 DM of sugarcane by cactus cladodes is recommended to maximise ruminal dynamics and parameters and to improve nutrient use in sheep.