Objective OA pathogenesis includes both mechanical and inflammatory features. Studies have implicated synovial fluid urate (UA) as a potential OA biomarker, possibly reflecting chondrocyte damage. Whether serum urate (sUA) levels reflect/contribute to OA is unknown. We investigated whether sUA predicts OA progression in a non-gout knee OA population. Methods Eighty-eight subjects with medial knee OA (BMI <33) but without gout were included. Baseline sUA was measured in previously banked serum. At 0 and 24 months, subjects underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs to determine joint space width (JSW) and Kellgren-Lawrence (KL) grades. Joint space narrowing (JSN) was determined as JSW change from 0 to 24 months. Twenty-seven subjects underwent baseline contrast-enhanced 3T knee MRI for synovial volume (SV) assessment. Results sUA correlated with JSN in both univariate (r=0.40, p≤0.01) and multivariate analyses (r=0.28, p=0.01). There was a significant difference in mean JSN after dichotomizing at sUA of 6.8 mg/dL, the solubility point for serum urate, even after adjustment (JSN of 0.90 mm for sUA≥6.8; JSN of 0.31 mm for sUA<6.8, p<0.01). Baseline sUA distinguished progressors (JSN>0.2mm) and fast progressors (JSN>0.5mm) from nonprogressors (JSN≤0.0mm) in multivariate analyses (area under the receiver operating characteristic curve 0.63, p=0.03; AUC 0.62, p=0.05, respectively). sUA correlated with SV (r=0.44, p<0.01), a possible marker of JSN, though this correlation did not persist after controlling for age, gender and BMI (r=0.13, p=0.56). Conclusions In non-gout patients with knee OA, sUA predicted future JSN and may serve as a biomarker for OA progression.