The main effects and synergy between three enzymes (phytase, xylanase and β-glucanase) on growth performance and nutrient digestibility was explored in Nile tilapia (Oreochromis niloticus). This was done according to a 2 × 2 × 2 factorial arrangement, resulting in 8 dietary treatments. In total 24 tanks (3 replicates per treatment) were used with 30 fish each (mean initial body weight 38 g (SD ± 0.8)). In a 42 day experiment growth and nutrient digestibility were measured. Fish were restrictively fed by hand twice daily. Phytase affected the nutrient digestibility, improving the ash, phosphorus and calcium digestibility. Neither individual enzymes supplementation, nor their combinations, did affect absolute growth (g/d). Averaged over diet, the feed conversion ratio (FCR) was low (0.92) despite 140 g/kg non-starch polysaccharides (NSP) in the diets. A comparison with previous studies, which used comparable diets and enzyme treatments was made to elaborate on the minor effects of enzyme supplementation in the present study. The response of fish fed the diet with phytase and xylanase was comparable between studies. However, the control treatments without enzymes in the present study had a lower FCR and higher dry matter (DM) and NSP digestibility compared to previous studies. The current control diet was more comparable to the diets supplemented with enzymes in previous studies. It is likely that in the present study, and other studies that do not show improvement in growth with the use of enzymes, the control diets were not sufficiently limiting in nutrients for growth.