A pilot study investigated whether CMKLR1 activation in human serum correlates with total chemerin levels in obese versus normal-weight individuals. Serum chemerin concentrations were higher in obese individuals (17.9 ± 1.8 nM) compared to normal-weight individuals (10.9 ± 0.5 nM), but CMKLR1 activation did not increase proportionally. The CMKLR1 activation/total chemerin ratio was lower in obese individuals (0.33 ± 0.04) compared to normal-weight individuals (0.58 ± 0.05). After breakfast, serum chemerin and CMKLR1 activation levels did not differ from baseline values. These findings suggest that increased total chemerin in obese individuals does not translate to increased CMKLR1 activation, indicating potential impaired processing or enhanced degradation of active chemerin in obese humans. The study highlights the importance of considering active chemerin forms rather than total chemerin concentrations when assessing chemerin signaling in obesity. The results emphasize the need for further research to understand the complex relationship between chemerin, its isoforms, and CMKLR1 activation in the context of obesity.A pilot study investigated whether CMKLR1 activation in human serum correlates with total chemerin levels in obese versus normal-weight individuals. Serum chemerin concentrations were higher in obese individuals (17.9 ± 1.8 nM) compared to normal-weight individuals (10.9 ± 0.5 nM), but CMKLR1 activation did not increase proportionally. The CMKLR1 activation/total chemerin ratio was lower in obese individuals (0.33 ± 0.04) compared to normal-weight individuals (0.58 ± 0.05). After breakfast, serum chemerin and CMKLR1 activation levels did not differ from baseline values. These findings suggest that increased total chemerin in obese individuals does not translate to increased CMKLR1 activation, indicating potential impaired processing or enhanced degradation of active chemerin in obese humans. The study highlights the importance of considering active chemerin forms rather than total chemerin concentrations when assessing chemerin signaling in obesity. The results emphasize the need for further research to understand the complex relationship between chemerin, its isoforms, and CMKLR1 activation in the context of obesity.