Background <p>Obesity is an increasingly alarming public health problem. Emerging evidence suggests that a dysregulation of sympathetic nervous system activity, particularly related to the adrenergic system, can play a role in the pathophysiology of obesity.</p> Objective <p>This systematic review explores the complex interplay between the adrenergic system and obesity.</p> Methods <p>PubMed, Web of Science and Scopus were searched until June 2023 using the following Boolean expression: (obese OR obesity) AND (adrenaline OR noradrenaline OR epinephrine OR norepinephrine). No time frame or other filters were set. Observational or interventional studies reporting plasma or urinary adrenaline and/or noradrenaline concentrations in adults with obesity were included.</p> Results <p>Among the 8680 studies, 35 met the eligibility criteria, comprising a total of 2588 subjects from which 1617 with general obesity or abdominal obesity. Despite some heterogeneity across studies, the evidence suggests a hyperadrenergic state in subjects with obesity, characterized by higher noradrenaline and lower adrenaline plasmatic concentrations, coupled with a blunted response to sympathetic stimuli, compared with their lean counterparts. Additionally, the adrenergic overdrive seems to be more pronounced when subjects with obesity are also diagnosed with obesity-associated comorbidities, except for hypertension. Abdominal fat weight loss interventions have a positive effect not only on reducing baseline noradrenaline levels, but also on restoring the impaired sympathetic response observed in subjects with obesity.</p> Conclusion <p>Overall, this systematic review highlights the complex interplay between catecholamines and obesity. It synthesizes current evidence and identifies key research gaps, thus providing valuable insights to guide future biomedical research and clinical practice.</p>