Common marmosets (Callithrix jacchus) are an important NHP model for the study of human aging and age-related diseases. However, the full potential of marmosets as a research model has not been realized due to a lack of evidence-based, standardized procedures for their captive management, especially regarding diet and feeding husbandry. In the present study, we conducted a high-resolution metabolomics analysis of plasma from marmosets from a 3-mo dietary crossover study to determine whether significant metabolic differences occur with a semisynthetic chemically defined (purified) diet as needed for controlled nutrition research. Marmosets were fed a standard, diverse-ingredient diet, followed by a semisynthetic purified diet, and then were switched back to the standard diet. The standard diet used in this analysis was specific to the animal facility, but it is similar in content to the diets currently used for other marmoset colonies. High-resolution metabolomics of plasma with liquid chromatography-mass spectrometry and bioinformatics was used to measure metabolic differences. The concentration of the essential amino acids methionine, leucine/isoleucine, lysine, and threonine were higher when marmosets were fed the purified diet. In contrast, phenylalanine concentrations were higher during exposure to the standard diet. In addition, metabolic pathway enrichment and analysis revealed differences among metabolites associated with dopamine metabolism and the carnitine shuttle. These results show that diet-associated differences in metabolism occur in marmosets and suggest that additional nutritional studies with detailed physiologic characterization are needed to optimize standard and purified diets for common marmosets.