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Metabolically healthy obesity (MHO) refers to obese individuals with a favorable metabolic profile, without severe metabolic abnormalities. This study aimed to investigate the potential of follistatin, a regulator of metabolic balance, as a biomarker to distinguish between metabolically healthy and unhealthy obesity. This cross-sectional study included 30 metabolically healthy and 32 metabolically unhealthy individuals with obesity. Blood samples were collected to measure the follistatin levels using an enzyme-linked immunosorbent assay (ELISA). While follistatin did not significantly differentiate between metabolically healthy (median 41.84 [IQR, 37.68 to 80.09]) and unhealthy (median 42.44 [IQR, 39.54 to 82.55]) individuals with obesity (p = 0.642), other biochemical markers, such as HDL cholesterol, triglycerides, C-peptide, and AST, showed significant differences between the two groups. Insulin was the most significant predictor of follistatin levels, with a coefficient of 0.903, followed by C-peptide, which exerted a negative influence at −0.624. Quantile regression analysis revealed nuanced associations between the follistatin levels and metabolic parameters in different quantiles. Although follistatin may not serve as a biomarker for identifying MHO and metabolically unhealthy obesity, understanding the underlying mechanisms that contribute to metabolic dysfunction could provide personalized strategies for managing obesity and preventing associated complications. [ABSTRACT FROM AUTHOR]