The objective of this study was to determine the effects of peripheral blood mononuclear cells (PBMC), derived from parasite-resistant St. Croix (STC) hair sheep and parasite-susceptible Suffolk (SUF) sheep, on Haemonchus contortus L stage larval death in vitro, with or without autologous serum. Larval morbidity was quantified by measuring larval ATP concentration following incubation with PBMC. Larvae exposed to either STC- or SUF-derived PBMC had lower ATP than live larvae (0.12 μmol/L ATP and 0.16 μmol/L ATP vs 0.27 μmol/L ATP, respectively) (P<.001) and greater ATP of dead larvae (0.03 μmol/L ATP) (P<.001). Breed differences were observed with addition of autologous serum. Larvae exposed to SUF-derived PBMC with autologous serum were not significantly different from live larval ATP. STC-derived serum did not significantly reduce larval ATP compared to PBMC alone (0.11 μmol/L ATP), but was significantly reduced compared to live larvae (0.22 μmol/L ATP) and SUF-derived PBMC with autologous serum (0.23 μmol/L ATP) (P<.001). These data indicate that a cellular response alone is capable of significantly reducing larval ATP in a breed-independent manner. However, addition of serum to SUF-PBMC failed to reduce larval ATP, indicating breed-dependent humoral response to H. contortus.