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(1) Adipsin is an adipokine that may link increased fat mass and adipose tissue dysfunction to obesity-related cardiometabolic diseases. Here, we investigated whether adipsin serum concentrations and adipose tissue (AT) <i>adipsin</i> mRNA expression are related to parameters of AT function, obesity and type 2 diabetes (T2D). (2) Methods: A cohort of 637 individuals with a wide range of age and body weight (Age: 18–85 years; BMI: 19–70 kg/m²) with (n = 237) or without (n = 400) T2D was analyzed for serum adipsin concentrations by ELISA and visceral (VAT) and subcutaneous (SAT) <i>adipsin</i> mRNA expression by RT-PCR. (3) Results: Adipsin serum concentrations were significantly higher in patients with T2D compared to normoglycemic individuals. We found significant positive univariate relationships of adipsin serum concentrations with age (r = 0.282, <i>p</i> < 0.001), body weight (r = 0.264, <i>p</i> < 0.001), fasting plasma glucose (r = 0.136, <i>p</i> = 0.006) and leptin serum concentrations (r = 0.362, <i>p</i> < 0.001). Neither VAT nor SAT <i>adipsin</i> mRNA expression correlated with adipsin serum concentrations after adjusting for age, sex and BMI. Independent of T2D status, we found significantly higher <i>adipsin</i> expression in SAT compared to VAT (4) Conclusions: Our data suggest that adipsin serum concentrations are strongly related to obesity and age. However, neither circulating adipsin nor <i>adipsin</i> AT expression reflects parameters of impaired glucose or lipid metabolism in patients with obesity with or without T2D.