Background: It is well known that plasma creatinine concentration is affected by muscle mass, while some studies have suggested cystatin C is affected by body mass index (BMI). Our aim was to assess the effects of lean versus fat mass on cystatin C and creatinine derivative equations in estimating glomerular filtration rate (GFR) in healthy young men. Methods: Three groups of participants were studied: those classified as normal (BMI 18-25 kg/m2 with body fat ,30%); muscular subjects (BMI .30 kg/m2 and body fat ,20%); and obese subjects (BMI .30 kg/m2 and body fat .30%). All underwent diethylenetriamine pentaacetic acid GFR, bio-electrical impedance and dual-energy X-ray absorptiometry body composition analysis, measurement of plasma cystatin C, creatinine and high-sensitivity C-reactive protein and completed a diet record. Results: Cystatin C was highest in the obese group (0.77 mg/L; 95% confidence intervals [CI] 0.69-0.77) and creatinine was highest in the muscular group (90.1 mmol/L; 95% CI 84.3-96.0). On multivariate analysis, body fat and GFR (P = 0.003) were significant determinants of cystatin C; muscle mass and age affected creatinine significantly (P = 0.02). Using cystatin C equations, Le Bricon and Hoek showed significantly lower estimated GFR in the obese group but performed reasonably well within 50%, 30% and 20% of GFR. Creatinine equations showed significant underestimations of GFR for the muscular group. Conclusions: Body fat is a significant determinant of cystatin C while creatinine concentration is highly affected by muscle mass and age. Body composition plays an important role in the interpretation of renal function. Cystatin C equations are still accurate in predicting GFR in our healthy male group without chronic kidney disease.