The objectives of this study were to determine differences in apparent total tract energy and macronutrient digestibility, fecal and urine characteristics, and serum chemistry of domestic cats fed raw and cooked meat-based diets and extruded diet. Nine adult female domestic shorthair cats were utilized in a replicated 3 × 3 Latin square design. Dietary treatments included a high-protein extruded diet (EX; 57% CP), a raw beef-based diet (RB; 53% CP), and a cooked beef-based diet (CB; 52% CP). Cats were housed individually in metabolic cages and fed to maintain BW. The study consisted of three 21-d periods. Each period included diet adaptation during d 0 to 16; fecal and urine sample collections during d 17 to 20; and blood sample collection at d 21. Food intake was measured daily. Total feces and urine were collected for determination of nutrient digestibility. In addition, a fresh urine sample was collected from each cat for urinalysis, and a fresh fecal sample was collected from each cat for determination of DM percentage and ammonia, short-chain fatty acid (SCFA), and branched-chain fatty acid (BCFA) concentrations. All feces were scored after collection using a scale ranging from 1 (hard, dry pellets) to 5 (watery, liquid that can be poured). Blood was analyzed for serum metabolites. Apparent total tract DM, OM, CP, fat, and GE digestibilities were greater (P ≤ 0.05) in cats fed RB and CB than those fed EX. Total fecal SCFA concentrations did not differ among dietary treatments; however, molar ratios of SCFA were modified by diet, with cats fed RB and CB having an increased (P ≤ 0.05) proportion of fecal propionate and decreased (P ≤ 0.05) proportion of fecal butyrate compared with cats fed EX. Fecal concentrations of ammonia, isobutyrate, valerate, isovalerate, and total BCFA were greater (P ≤ 0.05) in cats fed EX compared with cats fed RB and CB. Our results indicated that cooking a raw meat diet does not alter apparent total tract energy and macronutrient digestibility and may also minimize risk of microbial contamination. Given the increasing popularity of feeding raw diets and the metabolic differences noted in this experiment, further research focused on the adequacy and safety of raw beef-based diets in domestic cats is justified.