Simple SummaryThe nutritional composition of the diets for growing rabbits should be well-balanced, both to meet the requirements of the high-producing hybrids currently used and to avoid nutrient losses. The improvement of the feed conversion ratio represents a key point in increasing rabbit farmers’ profitability because of the high feeding costs. This study evaluated the growth performance, digestive efficiency and meat quality of growing rabbits belonging to the most diffused commercial crossbred rabbit breeds, Grimaud and Hyla, feeding them diets with different energy and protein levels. The two genotypes showed similar growth performance, but Grimaud rabbits achieved higher slaughter yield than Hyla rabbits. The administration of high-energy diets improved feed conversion and increased nutrient digestibility. Conversely, low dietary protein contents reduced nitrogen excretion without negative effects on growth, feed efficiency and carcass traits of fast-growing rabbits.The present study evaluated the effect of digestible energy (DE) and crude protein (CP) levels on growth, digestive efficiency, slaughter yield and meat quality in growing rabbits of two genotypes (Grimaud, G vs. Hyla, H). A total of 384 crossbred rabbits (192 G and 192 H), half males and half females, were divided into eight experimental groups according to a bi-factorial arrangement (2 genotypes × 4 diets; 48 animals/group) and reared in individual cages. From 33 to 64 days of age, rabbits were fed four diets obtained by combining two DE levels (high, HE—10.9 MJ/kg vs. low, LE—9.2 MJ/kg, on average) and two CP levels (high, HP—159 g/kg vs. low, LP—144 g/kg, on average). Then, all rabbits received the same fattening diet (10.7 MJ DE/kg; 156 g CP/kg) until slaughtering (77 days of age). Growth performance did not differ between genotypes for the entire trial (on average final live weight 3010 g; daily weight gain 50.5 g/d), but H rabbits showed a faster growth during the post-weaning period (p ≤ 0.01) compared to G rabbits, while exhibiting lower slaughter yield and lower carcass fatness (p ≤ 0.01). As DE level increased, feed intake decreased and feed conversion improved (p < 0.001), while caecal volatile fatty acid concentration increased and caecal pH and N-ammonia decreased (p ≤ 0.01). The reduction in the CP level did not affect performance and carcass traits. No significant interaction was detected between genotype and diet. In conclusion, G rabbits may have an advantage over H rabbits because of the higher slaughter yield. As for the nutritional characteristics of diets for high-producing crossbred rabbits, high energy levels are confirmed to enhance feed efficiency, whereas dietary CP can be reduced to 144 g/kg without negative effects on performance and carcass traits.