Food intake changes circulating metabolite concentrations. Thus, a comparison of circulating metabolites between dogs and cats is necessarily confounded by the composition of foods offered. The objective of this study was to determine differences between dogs and cats when given the opportunity to choose their own macronutrient intake. Four experimental foods with similar palatability, but varying in macronutrient content were prepared for dogs, and four for cats. Foods were available to dogs (=17) for food intake once a day and to cats (=27) at all times. Food 1 was high protein; Food 2 was high fat; Food 3 was high carbohydrates and Food 4 was balanced for macronutrients. By choosing a combination of foods, each animal could individually set its own macronutrient intake. Plasma metabolomics were determined after pets had consumed their food intake of choice for 28 days. Cats had higher concentrations of the essential amino acids histidine, isoleucine, phenylalanine and valine, but lower concentrations of lysine, methionine and threonine compared with dogs. Overall, non-essential amino acids were higher in cats. Regarding lipids, cats had increased concentrations of highly polyunsaturated fatty acids (PUFA) after 28 days, although arachidonic acid (AA) was consistently higher in dogs. Regarding circulating microbial metabolites, there was more stability for dogs compared with cats (none changed over time in dogs versus 42% changed in cats; <0.01). Concentrations of urea cycle intermediates, antioxidants and methylated compounds were also different between species. In conclusion, metabolite differences between dogs and cats reflected differences in species and food choices.