Obesity is an increasing problem in the equine population with recent reports indicating that the percentage o overweight horses may range anywhere from 20.6-51%. Obesity in horses has been linked to more serious healtl concerns such as equine metabolic syndrome (EMS). EMS is a serious problem in the equine industry given it defining characteristics of insulin dysregualtion and obesity, as well as the involvement of laminitis. Little re search however has been conducted to determine the effects of EMS on routine healthcare of these horses, ii particular how they respond to vaccination. It has been shown that obese humans and mice have decrease ! immune responses to vaccination. EMS may have similar effects on vaccine responses in horses. If this is the case these animals may be more susceptible to disease, acting as unknown disease reservoirs. Therefore, we in vestigated the effects of EMS on immune responses to routine influenza vaccination. Twenty-five adult horses o mixed-sex and mixed-breed (8-21 years old) horses; 13 EMS and 12 non-EMS were selected. Within each group 4 horses served as non-vaccinate saline controls and the remaining horses were vaccinated with a commercial ! available equine influenza vaccine. Vaccination (influenza or saline) was administered on weeks 0 and 3, am peripheral blood samples taken on week 0 prior to vaccination and on weeks 1, 2, 3, 4, and 5 post vaccination Blood samples were used to measure hemagglutination inhibition (HI) titers and equine influenza specific IgGa IgGb, and IgGT levels. Blood samples were also used to isolate peripheral blood mononuclear cells (PBMCs) fo analysis of cell mediated immune (CMI) responses via real-time polymerase chain reaction (RT-PCR). All horse receiving influenza vaccination responded with significant increases (P < 0.05) in HI titers, and IgGa and IgGl equine influenza specific antibodies following vaccination compared to saline controls. EMS did not significantl affect (P > 0.05) humoral immune responses as measured by HI titers or IgG antibody isotypes to influenz vaccination. There was an effect of metabolic status on CMI responses, with influenza vaccinated EMS horse having lower gene expression of IFN-y (P = 0.02) and IL-2 (P = 0.01) compared to vaccinated non-EMS contrc horses. Given these results, it appears that while metabolic status does not influence humoral responses to ai inactivated influenza vaccine in horses, horses with EMS appear to have a reduced CMI response to vaccinatioi compared to metabolically normal, non-EMS control horses.