The aim of the present study was to evaluate whether circulating serum ferritin and adiponectin (ADP) in the serum and synovial fluid correlate with cartilage damage severity assessed by arthroscopy in patients with knee osteoarthritis. The 40 subjects with symptomatic knee osteoarthritis were divided into four groups according to arthroscopy assessed cartilage damage, using Outerbridge (OB) grading. Group I included minor damage while Group IV included severe damage. Metabolic parameters, bone homeostasis, and insulin resistance markers were determined. Synovial fluid of the affected knee joint was obtained and assessed for synovial adiponectin levels. Parameters of bone homeostasis in the serum including levels of PTH, alkaline phosphatase, 25OH vitamin D, serum calcium and phosphorus were similar in the four groups. A significant difference in the level of serum ferritin was found: ferritin levels increased from Group 1 to Group 4 in a continuous fashion (p < 0.035). In General linear model (GLM) analysis significant by-group differences in circulating ferritin persisted even after adjustment (p = 0.030). Although all groups were similar in terms of serum ADP levels, between groups difference in synovial fluid ADP was found (p < 0.037). However, after controlling for the age, there was no between-group difference in terms of synovial ADP levels. Serum ferritin levels were associated with cartilage damage severity assessed by arthroscopy. This association was independent of age, sex, BMI, and CRP levels suggesting that ferritin may be actively involved in the progression of cartilage damage in patients with symptomatic knee OA.