Purpose: Myokines secreted from skeletal muscle such as irisin, osteokines secreted from bone such as osteocalcin, and hepatokines secreted from the liver such as fibroblast growth factor 21 (FGF21) play a role in the regulation of metabolic homeostasis. However, the changes that occur in obesity and the interaction between them have not been fully explained. Therefore, this study aimed to compare irisin, osteocalcin and FGF21 levels in young obese males against individuals with normal body weight and to reveal the possible relationship between them and with anthropometric measurements and blood lipid profile. Materials and methods: This single-center study included 28 Turkish young males aged 20–29 years: 14 obese participants with a body mass index (BMI) between 30.0 and 34.9 and 14 healthy controls with a BMI between 18.5 and 24.9. Anthropometric, and body composition parameters, blood lipid profile, and irisin, osteocalcin and FGF21 levels of groups were measured. Correlation analyses were performed between irisin, osteocalcin, and FGF21 and other measured parameters. Results: Circulating irisin, osteocalcin and FGF21 levels were significantly higher in the obese group than in the control group (p ​< ​0.05). Correlation analysis showed that irisin was positively correlated with total cholesterol, triglycerides and low density lipoprotein-cholesterol (LDL-C) and FGF21 was positively correlated with total cholesterol and LDL-C (p ​< ​0.05). Positive correlation between irisin and osteocalcin, FGF21 and osteocalcin and FGF21 and irisin was observed (p ​< ​0.05). Conclusions: Irisin, osteocalcin, and FGF21 have a potential role in the pathophysiology of obesity and related metabolic diseases due to their interactions.