Objective: Overweight and obesity are ranked as the fifth leading cause for global deaths and significantly contribute to nonalcoholic fatty liver disease (NAFLD), a common comorbidity finally leading to end-stage liver disease. The diagnostic tool for confirming NAFLD is liver biopsy, an invasive procedure known to cause complications. Results from transient elastography are not reliable in obese patients. Therefore, alternative diagnostic approaches are necessary. One putative biomarker is fetuin-A, also known as α 2 -Heremans-Schmid Glycoprotein (AHSG), which has been proposed for the diagnosis of NAFLD. We therefore aimed to examine the role of fetuin-A in severely obese patients and its value in predicting NAFLD.Methods: 62 obese patients with a body mass index of at least 30 kg/m² undergoing a medically supervised weight loss program were analysed at time points T0 (before weight loss), T1 (after non-surgical weight loss within 12 weeks), and T2 (after 52 weeks). Anthropometrical parameters, laboratory values for NAFLD, fetuin-A, "Fatty Liver-index" (FLI), and NASH-Score were determined.Results: 38 out of 62 patients completed the program. These patients showed a significant decrease in BMI (T0: 41.5 ± 7.1 kg/m²; T2: 33.5 ± 7.0 kg/m²; p<0.001 each). While markers of NAFLD improved from T0 to T2, no significant change was observed in fetuin-A (p=0.36). FLI and NASH-Score significantly improved over time (p ≤ 0.001; p=0.03). Both scores failed to show a correlation with fetuin-A at baseline or during the program. Conclusion:Fetuin-A does not appear to be suitable for diagnosis and follow-up of NAFLD in patients with severe obesity.