Impaired virus-specific immune responses have previously been observed with Schistosoma mansoni coinfection. We characterized Gag-specific responses in HIV-1-positive Ugandans with and without S. mansoni coinfection. We observed no significant difference in the frequency of IFN-gamma CD8+ T cells between the two groups. Interestingly, expression of CD107, a marker for cytolytic activity, was significantly lower in volunteers with S. mansoni coinfection compared with those with HIV-1 infection alone (p = 0.002). In contrast, the frequency of IL-10-positive Gag-specific CD8+ T cell responses was higher in volunteers with S. mansoni coinfection (p = 0.004). Analysis of human CMV-specific CD8+ T cell responses in the same individuals failed to reveal a similar pattern of altered CD107 and IL-10 expression. Our results suggest that S. mansoni coinfection is associated with decreased Gag-specific CD8+ cytolytic T cell responses and increased number of Gag-specific IL-10 positive CD8+ T cells. Our findings may have important implications toward the implementation of HIV preventive and therapeutic programs in Africa.