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Diets with moderate levels of nonstructural carbohydrates (NSCs) elevate plasma lipopolysaccharide (LPS) at 2 hours and interleukin-1β (IL1B) at 1 hour postprandially. It is possible that rapid fermentation of NSC in the digestive tract lowers the pH, inducing inflammation. DigestaWell buffer, a bicarbonate-containing dietary supplement, may mitigate changes in LPS and IL1B through pH buffering. Six mature geldings, in a crossover design, consumed a feed providing 1.2 g/kg bodyweight of NSC. Plasma glucose, insulin, LPS, IL1B, and d-lactate were analyzed from samples obtained at −0.5, 1, 2, 4, 6, and 8 hours postfeeding. Whole blood was analyzed for pH and TCO2. Plasma glucose and insulin increased postprandially (P < .001); however, insulin responses were lower in horses receiving buffer (P = .017). The buffer also reduced plasma concentrations of IL1B (P = .039) compared to controls. Concentrations of d-lactate (P = .022) and LPS (P = .004) were affected by the time by treatment interaction, whereby control horses had higher concentrations of d-lactate at 2, 4, and 8 hours (P < .02) and LPS at 2, 4, 6, and 8 hours (P < .05). Meal consumption reduced blood pH (P = .011); however, pH was higher in horses receiving buffer (P = .012). Blood TCO2 levels remained <37 mmol/L but tended to be higher in horse receiving buffer (P = .081). Given these findings, we believe that DigestaWell buffer mitigates the negative effects of rapid NSC fermentation in the equine digestive tract, evidenced by reduced postprandial LPS and IL1B.A bicarbonate containing dietary supplement, DigestaWell buffer, prevented a postprandial rise in plasma interleukin-1β.Consumption of moderate amounts of nonstructural carbohydrates transiently reduces plasma pH.DigestaWell buffer reduced plasma d-lactate concentrations at 2–4 hours postmeal consumption.