We describe the use of nuclear magnetic resonance metabolomics to analyze blood serum samples from healthy individuals (n = 26) and those with metastatic colorectal cancer (CRC; n = 57). The assessment, employing both linear and nonlinear multivariate data analysis techniques, revealed specific metabolite changes associated with metastatic CRC, including increased levels of lactate, glutamate, and pyruvate, and decreased levels of certain amino acids and total fatty acids. Biomarker ratios such as glutamate‐to‐glutamine and pyruvate‐to‐alanine were also found to be related to CRC. The study also found that glutamate was linked to progression‐free survival and that both glutamate and 3‐hydroxybutyrate were risk factors for metastatic CRC. Additionally, gas chromatography coupled to flame‐ionization detection was utilized to analyze the fatty acid profile and pathway analysis was performed on the profiled metabolites to understand the metabolic processes involved in CRC. A correlation was also found between the presence of certain metabolites in the blood of CRC patients and certain clinical features.