Objective To describe the associations between body composition and hormonal and inflammatory factors measured 5 years prior and tibial cartilage volume in young adults, and to explore if these factors contribute to the sex difference in tibial cartilage volume. Methods Subjects broadly representative of the young adult Australian population (n = 328, ages 31-41 years, 47.3% women) were selected. They underwent T1-weighted fat-suppressed magnetic resonance imaging (MRI) of their knees. Tibial cartilage volume was measured from MRI. Sex hormone binding globulin (SHBG) and testosterone in a subset of women and C-reactive protein (CRP) level and fibrinogen in both sexes were measured 5 years prior. Body mass index (BMI), fat mass, and lean mass were calculated from height, weight, and skinfolds. Results In multivariable analyses, correlates of tibial cartilage volume included lean body mass (β = 26.4 mm3; 95% confidence interval [95% CI] 13.6, 39.1), fat mass (β = -11.8 mm3; 95% CI -22.2, -1.4), and fibrinogen (β = -146.4 mm3; 95% CI -276.4, -16.4), but not BMI, testosterone, or CRP level. In women, SHBG was positively associated with tibial cartilage volume (β = 0.67 mm3; 95% CI 0.14, 1.20) and Free Androgen Index was negatively associated with lateral tibial cartilage volume (β = -0.04 mm3; 95% CI -0.07, 0.00). Men had 13% more tibial cartilage volume (500 mm3) than women. The magnitude of this association decreased by 38%, 20%, and 37% after adjustment for lean body mass, fat mass, and fibrinogen, respectively. Conclusion Body composition, sex hormones, and fibrinogen correlate with knee cartilage volume in young adult life. Sex difference in knee cartilage volume is contributed largely by variations in body composition and/or fibrinogen.