The duck and chicken are important hosts of avian influenza virus (AIV) with distinctive responses to infection. Frequently, AIV infections in ducks are asymptomatic and long-lasting in contrast to the clinically apparent and transient infections observed in chickens. These differences may be due in part to the host response to AIV infection. Using real-time quantitative PCR, we examined the expression of immune-related genes in response to low pathogenic AIV H11N9 infection in peripheral blood mononuclear cells (PBMC) isolated from the blood of chickens and Pekin ducks. While chicken PBMC expressed IL-1beta and IL-6 at high levels similar to mammalian species, duck PBMC expression levels were minimal or unchanged. Similarly, duck IFN-beta expression was nearly unaffected, whereas chicken expression was highly upregulated. Chicken IFN-gamma was expressed to higher levels than duck IFN-gamma, while IFN-alpha was expressed similarly by both species. IL-2 was elevated early in infection in duck PBMC, but returned to baseline levels by the end of the experiment; in contrast, IL-2 was weakly induced in chicken PBMC at late time points. TLR-7 and MHC class I molecule expressions were conserved between species, whereas duck MHC class II expression was downregulated and chicken expression was unchanged. These results show distinct PBMC expression patterns of pro-inflammatory cytokines and IFNs between species. The differences in pro-inflammatory cytokine and IFN expression reflect the asymptomatic and lasting infection observed in ducks and the tendency towards clinical signs and rapid clearance seen in chickens. These results highlight important differences in the host response to AIV of two species thought to be critical in the genesis and maintenance of epidemic strains of AIV.