Chronic kidney disease is a common finding in older captive exotic felids. The purpose of this study was to evaluate the effectiveness of a probiotic to reduce blood urea nitrogen and creatinine in large felids. Fifteen adult, large felids (6 tigers [Panthera tigris], 5 lions [Panthera leo], 3 cougars [Puma concolor], and 1 leopard [Panthera pardus]) were administered a probiotic twice daily after a baseline complete blood cell count and plasma chemistry panel was obtained. Plasma chemistry values were rechecked at 2 mo (n = 14) and 6 mo (n = 9). There was no significant change in blood urea nitrogen over time; however, there was a significant change in creatinine over time (P = 0.04). Creatinine concentration decreased significantly between 2 and 6 mo (P = 0.02), and a decrease was seen between 0 and 6 mo, but this change was not significant (P = 0.05). There was no significant difference noted for creatinine concentration between 0 and 2 mo (P = 0.35). This probiotic may be helpful in large felids with elevated creatinine concentrations because of chronic kidney disease; however, further studies are warranted.