Utilizing metabolomics, a tool for measuring and characterizing low-molecular-weight substances (LMWs), to identify eventual changes in response to dietary intervention is novel in cats with chronic kidney disease (CKD), a condition characterized by retention of uremic solutes. This study aims to assess the serum metabolomic profile of cats in early stages of CKD and to compare the serum metabolomic of CKD cats after 60 days of a renal diet to evaluate the effect of dietary intervention on these metabolites. Twenty-five domestic cats were included in the study. Fifteen cats with CKD stages 1 (n = 6) and 2 (n = 9) according to the International Renal Interest Society (IRIS) were included in the renal groups, and a control group consisting of 10 cats was included. All animals were enrolled on a maintenance diet for 30 days before the experimental period. The metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS). Partial least squares discriminant analysis (PLS-DA) was performed on Metaboanalyst 4.0 software. Forty-three metabolites were identified. Citric acid and monostearin were altered in the CKD2 group when compared to CKD1 and the control group at T0. A total of seven serum metabolites differed after 60 days of the renal diet: glycine, fructose, glutamic acid, arachidonic acid, stearic acid, creatinine, and urea. Changes were seen in the serum metabolomic profile after 60 days of the renal diet, and some of the metabolites that changed in response to the diet have beneficial effects on health. Overall, metabolomics markers have the potential to identify early stages of CKD, providing insights into the possible pathophysiologic processes that contribute to the development and progression of CKD.