This study was conducted to investigate the effects of dietary N sources and nisin on nutrient digestibility, rumen fermentation, N utilization, growth performance, and plasma metabolites in growing lambs. Thirty-two male Hu lambs (23.1 ± 1.66 kg initial BW) were assigned to 4 dietary treatments in a randomized block design with a 2 × 2 factorial arrangement. Two N sources, soybean meal (SBM) and distillers dried grains with solubles (DDGS), and 2 levels of nisin, 0 and 30.5 mg of nisin/kg of diet, were used to formulate 4 diets. Growth performance of lambs fed with different N sources diet responded differently with time. From wk 1 to 4, DDGS resulted in lower DMI and ADG than SBM (P < 0.05), but G:F was not affected (P > 0.05). In contrast, from wk 5 to 8, DDGS did not affect DMI or ADG (P > 0.05) but resulted in a higher G:F than SBM (P < 0.05). In wk 4, the SBM-fed lambs had a trend to increase BW relative to those fed DDGS (P = 0.07), while the final BW did not differ between SBM and DDGS (P > 0.05). Ruminal acetate, butyrate, and BCVFA concentrations were greater (P < 0.05) and total VFAs concentrations tended to be greater (P = 0.08) for the SBM-fed lambs than for the DDGS-fed lambs. The SBM-fed lambs had higher ruminal ammonia-N, BUN, and urinary N excretion than those consuming DDGS (P < 0.05), while N retention was similar between SBM and DDGS (P > 0.05). Compared with the DDGS-fed lambs, SBM-consuming lambs had higher DM, OM, and CP but lower ADF digestibility (P < 0.05). Nisin supplementation did not affect growth performance, rumen fermentation, nutrient digestibility, plasma metabolites, or N utilization (P > 0.05). It was concluded that DDGS can substitute SBM to grow Hu without adverse effects on animal performance and to reduce production cost, but nisin supplementation probably has little no benefits.