Chemokine (C-X-C motif) ligand-14 (CXCL14) levels are downregulated in experimental rodent models of obesity. Moreover, CXCL14 reportedly favors insulin sensitization in obese mice. Here we examined, for the first time, the role of CXCL14 in human obesity. We found that circulating levels of CXCL14 were decreased in patients with obesity and, especially, those with concomitant type-2 diabetes. CXCL14 levels were negatively associated with BMI and with indices of impaired glucose/insulin homeostasis. CXCL14 expression was decreased in subcutaneous adipose tissue from patients with obesity and type-2 diabetes. In adipose tissue, CXCL14 expression was negatively correlated with the expression of genes encoding pro-inflammatory molecules, and positively correlated with GLUT4 and adiponectin expression. In conclusion, obesity, and especially, concomitant type-2 diabetes are associated with abnormally decreased levels of CXCL14 in blood and impaired CXCL14 expression in adipose tissue. CXCL14 downregulation may be a novel biomarker of altered metabolism in obesity. CXCL14 also deserves further research as a therapeutic candidate.