The main objective was to determine the immune response of Blackbelly lambs infected with Haemonchus contortus, Trichostrongylus colubriformis, or both species. In the first stage, an experimental challenge was performed with 200 infective larvae (L3)/kg body weight (BW) of H. contortus (Hct, n = 8). Additionally, eight animals were infected with 500 L3/kg BW of T. colubriformis (Tcl), eight lambs with the mixed infection at the same dose (HctTcl), and lambs without infection were the control group. In the second infection, the same lambs were reinfected with high doses: 400 L3/kg BW of Hct and 900 L3/kg BW of Tcl. The third stage consisted of a natural reinfection in grazing. Faecal samples were taken to determine the faecal egg count (FEC) of gastrointestinal nematodes (GINs). IgA was determined in serum and saliva by an indirect Enzyme-Linked Immuno Sorbent Assay (ELISA). The haematological parameters were recorded. With the first challenge, it was not possible to promote an immune response, whereas in the second infection, FEC were higher than 1000 eggs per gram of faeces (EPG) in infected animals. During the third stage, FECs were higher in lambs infected with Tcl. Eosinophils (EOS) did not show differences in the first and second stages, but during grazing the infected lambs had higher counts than the control group (P < 0.05). IgA activity values showed the same trend, and lambs infected with HctTcl had a higher response (33% of the positive standard) than groups mono-infected (16.5% and 22.6%, respectively).