Nutrient digestibility in distillers dried grains with solubles (DDGS) is limited by physical constraints such as particle size and by biochemical limitations such as phytate and fiber or nonstarch polysaccharides (NSP). To determine the separate effects of these limitations on nutrient digestibility, ground DDGS (383 µm) supplemented with phytase (0 or 250 units/kg of feed) and xylanase (0 or 4,000 units/kg of feed) was evaluated in a 2 × 2 factorial arrangement of treatments together with unground DDGS (517 µm) and an N-free diet in a 6 × 6 Latin square. Cofermented wheat and corn DDGS contained 8.6% moisture, 31.0% CP, 1.04% Lys, 8.0% ether extract, 2.0% starch, 40% NDF, and 0.85% P (as-is basis). Diets contained 43.7% DDGS as the sole source of AA; the digesta from pigs fed the N-free diet served to subtract basal endogenous AA losses and as control for energy digestibility. Six ileal-cannulated barrows (37.1 ± 0.8 kg of BW) were fed 6 diets at 2.8 × maintenance for DE in six 9-d periods. Feces and ileal digesta were collected for 2 d each. The apparent ileal digestibility (AID) of GE and apparent total tract digestibility (ATTD) of GE and NDF were 2.3, 0.5, and 5.1%-units greater (P < 0.05) for the ground than unground DDGS diet, respectively. Consequently, the ATTD of GE was 1.3%-units greater (P < 0.05) and the DE content was 0.06 Mcal/kg greater (P < 0.05) for ground than unground DDGS, respectively. Grinding of DDGS did not affect (P > 0.05) the ATTD of crude fiber, ADF, P, and Ca in diets. Grinding of DDGS increased (P < 0.05) the AID of most AA in diets including Lys, Met, and Thr by 6.9, 1.1, and 1.7%-units, respectively. Grinding of DDGS increased (P < 0.05) the SID of Lys by 6.2%-units and SID content of Lys and Thr by 0.06 and 0.02%-units, respectively. Phytase and xylanase did not interact (P > 0.05) to affect nutrient digestibility. Phytase increased (P < 0.001) the ATTD of P by 10.5%-units, but did not affect (P > 0.05) AA digestibility. Xylanase did not affect nutrient digestibility. In conclusion, particle size is an important physical characteristic affecting digestibility of energy and AA, but not P in DDGS. Phytate in DDGS limits digestibility of P, but not energy and AA. The substrate for xylanase in DDGS did not hinder energy and AA digestibility.