Chemokine receptors such as C-C chemokine receptor 5 (CCR5) are activated through interaction with their ligands and are well known for their role in chemotaxis and signal transduction. While serving these roles, cellular responses are effected, hence the immune function of these molecules is established. Given the role of CCR5 in immune function and that the immune and metabolic systems are interlinked, subsequent immune-directed changes should be measurable at a metabolic level. Numerous investigations have reported on metabolic changes associated with CCR5 status in the presence of disease, so as to understand whether specific CCR5 genotypes, frequency and/or levels offer protection to the host or not. However, these metabolic changes were recorded using older conventional techniques. Depending on certain factors such as the disease model, the geography of the samples and/or the ethnic group under study, the role of CCR5 in disease differs. In addition, little is known about CCR5’s role in the absence of an enhanced inflammatory state, such as when infection persists. Metabolomics is defined as the study of metabolites and informs on metabolic changes within living organisms as induced by various stimuli, such as the interaction of CCR5 with its ligand. Since metabolomics reflects the underlying biochemical activity and state of cells/tissues, this review proposes it as a tool to clarify the contrasting roles of CCR5.