Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide, presenting poor long-term outcomes and chronic disability. COPD is a condition with a wide spectrum of clinical presentations because its pathophysiological determinants relate to tobacco smoke, genetic factors, alteration of several metabolic pathways, and oxidative stress. Consequently, patients present different phenotypes even with comparable degrees of airflow limitation. Because of the increasing social and economic costs of COPD, a growing attention is currently paid to "omics" techniques for more personalized treatments and patient-tailored rehabilitation programs. In this regard, the systematic investigation of the metabolome (i.e., the whole set of endogenous molecules) in biomatrices, namely metabolomics, has become indispensable for phenotyping respiratory diseases. The metabolomic profiling of biological samples contains the small molecules produced during biological processes and their identification and quantification help in the diagnosis, comprehension of disease outcome and treatment response. Exhaled breath condensate (EBC), plasma and serum are biofluids readily available, with negligible invasiveness, and, therefore, suitable for metabolomics investigations. In this paper, we describe the latest advances on metabolomic profiling of EBC, plasma and serum in COPD patients.