This study was carried out to evaluate the immune response and the impact of Trichostrongylus colubriformis infections on the performance of growing Santa Ines lambs. Thirty male lambs, 3-4 months of age, were maintained in individual pens and restrictively randomised by weight into 3 treatment groups: (1) infected group, artificially infected with 2500 T. colubriformis larvae, three times a week, for 13 weeks, and fed ad libitum; (2) Pair-Fed Group, non-infected and fed with the same amount of food consumed by the infected animal of the same class on the previous day; and (3) control group, non-infected and fed ad libitum. Refused feed was weighed daily to assess the food intake of each lamb. Animals were weighed weekly and blood and fecal samples were collected. At the end of the trial, all lambs were euthanized to determine worm burden and collect intestinal tissues and mucus samples for histological and immunological analysis. The infected group presented eosinophilia, increased number of inflammatory cells in the mucosa, in addition to an increased production of specific immunoglobulins against T. colubriformis, which partially prevented the establishment of infective larvae. As a consequence of parasitism, the infected lambs presented reduced serum albumin concentrations and demonstrated severe small intestine lesions, such as villous atrophy and epithelial erosion, which impaired the digestion and absorption of nutrients, causing a significant loss in performance. The infected group presented a 37% reduction in daily weight gain (107.26 ± 10.8 g/day), when compared with the control group (171.07 ± 7.15 g/day). The infected lambs also demonstrated the worst food conversion, i.e., each animal needed to consume on average 10.05 ± 0.52 kg of food to gain 1 kg live weight. The voluntary hay intake depression in infected animals was small, and statistical difference (P<0.01) was seen only on two occasions (ninth and 12th weeks), in comparison with the control group. In conclusion, Santa Ines lambs infected with T. colubriformis demonstrated a reduction in performance, caused by the damages produced by the adult nematodes in intestinal mucosa, and also by the immunopathological changes associated with the infection.