The presence of β-mannans in feed can produce a futile and chronic immune stimulation in fattening pigs. In this trial, a 1-4-endo-D-β-mannanase was added to the feed (HC) during growth and fattening (0.03% of Hemicell HT) and physical performance and pathological data were recorded, and intestinal integrity and immune activation were studied by molecular biomarkers, compared to a control group (CON). The treatment diet was reduced in energy content by 40 Kcal/kg NE. From each group, 113 and 112 animals housed in 8 pens were individually identified and weighed three times: at 7th, 63rd and 116th days in feed. The FCR was calculated for groups of two pens and ADG individually. There was no difference in ADG (CON = 0.836, HC = 0.818) nor in FCR between groups (p = 0.486). During growth, there was a higher frequency of normal feces in HC and there were also no differences in the frequency of gastric lesions. A significant increase in Claudin, Occludin, IFN-γ and IL8 was observed in the CON in feces and a significant decrease in IL-6 in HC. In tissues, there were differences for IL-12p40, TNF-alpha in jejunum (increased CON) and TGF-β in ileum and jejunum, (decreased HC). The economic performance was EUR 4.7 better in the treated group. In conclusion, the addition of 1-4-endo-D-β--mannanase to the feed with a 1.6% reduction in net energy compared to the control, allowed the animals to perform as well as the animals on the higher energy diet, with lower prevalence of diarrhea.