Upon infection the protozoan parasite Toxoplasma gondii induces a strongly polarized Th1 cytokine response, necessary for effector differentiation of CD8 lymphocytes. Conversely, pre-infection with an intestinal nematode, such as Heligmosomoides polygyrus has been shown to attenuate immune responses to intracellular pathogens and inhibit the development of Th1 responses. Previous studies have shown that mice co-infected with H. polygyrus and T. gondii exhibit suppressed CD8+ T cell responses against T. gondii, however the precise mechanism by which co-infection impinges upon the priming and differentiation of antigen-specific T cells remains to be determined. Using a novel Kb-peptide tetramer-binding assay for Tgd057-reactive CD8+ T cells, we show that co-infected mice develop a diminished antigen-specific response to T. gondii. Co-infected mice develop fewer antigen-specific CD8+ T cells, a decreased fraction of terminally differentiated effector cells, and reduced effector IFN-γ production. Furthermore, terminally differentiated antigen-specific effector T cells (CD62Llo, KLRG1+) from co-infected mice retain an intrinsic defect in cytokine production. Helminth infection blocked IL-12 responses of CD8α+ dendritic cells to T. gondii, indicating that rather than inhibiting CD8+ T cell priming itself, the principal effect of helminth infection is to attenuate the differentiation of effector lymphocytes by inhibiting critical innate cytokine responses.