The use of plant by-products in aqua-feeds contributes to improving the sustainability of aquaculture, but also leads to increased levels of undesirable non-starch polysaccharides (NSP) and phytate. NSP-degrading enzymes (i.e. xylanase) and phytase can be used as a tool to deal with NSP and phytate. A feeding trial was conducted to test whether the effects of phytase and xylanase supplementation on growth performance and nutrient digestibility in Nile tilapia are dependent on diet quality. Two diets were formulated, a control quality (CQ diet; 36% protein and 17% NSP) and a low quality diet (LQ diet; 32% protein and 30% NSP). The difference in diet quality was created by using higher levels of wheat bran, rapeseed meal, sunflower meal, rice bran and wheat dried distiller's grain with solubles in the LQ diet. Both diets had the following enzyme treatments: 1) no enzymes, 2) phytase, and 3) phytase and xylanase. Phytase (Buttiauxella sp.) was supplemented at ca. 660 FTU/kg and xylanase at ca. 6596 U/kg. In total, 18 tanks (6 treatments, 3 replicates per treatment) were used with 30 fish each (mean initial body weight 39 g). Fish were restrictively fed at 80% of expected satiation for 42 days, by hand twice daily. Growth was determined by batch weighing of the fish at the start and at the end of the trial. Faeces were collected non-invasively using settling units in order to determine the nutrient digestibility, using yttrium as an inert marker. Fish fed the LQ diet had lower growth (1.35 g/d vs. 1.52 g/d) and nutrient digestibility (except for calcium and ash), compared to the CQ diet (P <.05). Phytase improved the digestibility of dry matter, total carbohydrates, NSP, energy, ash, phosphorus and calcium (P <.01) Phytase improved growth (g/d) by ca. 7% and phosphorus availability by ca. 29%. The improvement in growth with phytase was comparable between the two diets, improving the FCR from 1.04 to 0.97 and from 1.17 to 1.10 for the CQ and LQ diet, respectively. Xylanase supplementation, on top of phytase, did not enhance growth (P >.05). Xylanase improved digestibility of dry matter, energy, total carbohydrates and NSP (from 29.7% to 36.6%) of the LQ diet, but not of the CQ diet (interaction; P <.05). In conclusion, the effect of phytase on improved nutrient digestibility and performance was independent of diet quality, whereas the effect of xylanase was dependent on diet quality.