The objective was to evaluate the effects of dietary mannan and β-mannanase supplementation on growth performance and serum acute phase proteins in nursery pigs. Pigs (n = 480) were blocked by initial BW (6.6 ± 0.4 kg) and 12 pens per treatment were randomly assigned to 1 of 4 treatments in a 2 x 2 factorial arrangement for 28 d. Two levels of dietary mannan (0.4% vs 2.8%) were offered with and without 0.05% endo-1,4-β-mannanase. Serum was collected (1 pig/pen) for haptoglobin and C-reactive protein (CRP) analysis on d 0 and d 28. There were no significant interactions between mannan level or β-mannanase supplementation. High mannan decreased ADG (P = 0.027) and ADFI (P = 0.024) compared to low mannan diets with no effect of β-mannanase (P > 0.10). Haptoglobin and CRP were not affected by mannan level or β- mannanase supplementation (P ≥ 0.160). Therefore, dietary β-mannans as high as 2.8% did not induce a systemic innate immune response. Thus the levels of β-mannan found in practical diets (< 2%) are unlikely to induce an immune response, so supplementation with β-mannanase to avoid this response is not warranted.