Abstract Oenothein B is an ellagitannin isolated from the Epilobium angustifolium plant, which has been shown to have immunomodulatory properties. This compound is known to activate myeloid cells, αβ T cells, and innate lymphocytes, such as NK cells, NKT cells, and γδ T cells. Previous work from our laboratory showed that oenothein B primes and enhances the production of interferon-γ by human and bovine NK cells in response to secondary stimuli, including tumor cells and IL-18. Here, we examined whether oenothein B enhances the response of innate lymphocytes to various pathogen associated molecular patterns. We found that oenothein B enhanced interferon-γ production by bovine peripheral blood mononuclear cells in response to several pathogen associated molecular patterns, including the Toll-like receptor 3 agonist poly I:C. We have also found that intranasal administration of oenothein B to mice before infection with influenza can reduce the morbidity of the infection. Our preliminary results suggest that oenothein B is capable of enhancing innate immunity against viral infections, possibly through the enhanced production of interferon-γ by NK cells. The effect of oenothein B on the antiviral activity, including interferon-γ production, of innate lymphocytes during viral infection is currently under investigation in both human cells and mouse models. This work is funded by NIH NCCAM P01 AT004986 and P20 GM103500.