Mastitis is one of the costliest diseases in the dairy cattle industry. Environmental pathogens, such as Streptococcus uberis (Strep. uberis), are the most prevalent causes of mastitis infections, while contagious pathogen mastitis has declined in incidences due to improvement in management protocols. Antimicrobials and antibiotics are the primary therapies currently utilized in the dairy industry to treat mastitis. However, the concern for antibiotic overuse and potential bacterial resistance due to improper use of these therapies has steered research in exploration of alternatives to antibiotics or other strategies. One potential alternative is supplementation of an immunomodulatory feed additive to daily cattle total mixed rations (TMR). A current immunomodulator is OmniGen-AF ® (OMN) produced by Phibro Animal Health Corporation (Teaneck, NJ) and has been explored being fed to lactating dairy cattle by previous research groups. OmniGen- AF ® has been reported to improve initial innate immune response during infection. However, it is unknown how OMN influences the innate immune system in vivo to a S. uberis mastitis infection. The ability of OMN to modulate immune function during an environmental mastitis infection was tested compared to control groups. Cows fed OmniGen-AF® and challenged with Strep. uberis had numerically higher least squared mean Log somatic cell count compared to the control group that was not fed OMN and challenged with Strep. uberis. OMN fed cows displayed numerically higher average daily feed intake and fluid milk yield values compared to the control group. Further analysis of milk and blood samples using immunoassays to monitor the effects OMN has on cytokine and cortisol levels throughout mastitis infection is needed to determine innate immune response. In conclusion, OmniGen-AF® has the potential as an immunomodulator that improves innate immune system activity with continuous supplementation in the diet to prevention of dairy cattle environmental mastitis.