The carnivorous nature of the domestic cat makes feline metabolism of carbohydrates unique. The cats' glycemic response has been previously studied, with variable outcomes in response to carbohydrate level and source, but is an important response to understand how to control glycemia. The objectives of this study were to determine the glucose and insulin responses of cats fed 3 commercial diets differing in carbohydrate content and source, and to investigate the effects of diet on RQ, energy expenditure (EE), and glycemic response. Domestic shorthair cats (=19, 10 males, 9 females) of similar age (4.3 ± 0.48 yr, mean ± SD) and of ideal body condition score were used. Cats were fed, once a day, 1 of 3 commercial diets that differed in their perceived glycemic response (PGR; 36.8%, 30.7%, and 23.6% starch for high, medium, and low PGR, respectively) with cats cycling through all diets in 3 periods in 6 complete and 1 incomplete 3 × 3 Latin square. Each period consisted of 8 d of adaptation to the diet, followed by 21-h calorimetry measurements, and real-time interstitial glucose measurements on day 9. On day 10, sequential blood sampling was completed to determine blood glucose and insulin. BW and ME intake did not differ among treatments. EE in the fasted state did not differ among treatments (P = 0.160), whereas postprandial EE was highest for the high PGR diet compared with the medium PGR and low PGR diets (P < 0.001). In conclusion, cats revealed a prolonged postprandial glucose and insulin response compared with other monogastric animals, yet diet effects were minimal. Overall, interstitial glucose measures were less variable than serum glucose measurements and followed a parallel pattern to RQ. Therefore, going forward, calorimetry and continuous interstitial glucose monitoring should be considered as less invasive alternatives to repeated blood sampling.