Background: Urate and homocysteine are potential biomarkers for disease progression in Parkinson's disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown. Objectives: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD. Methods: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson's Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations. Results: Baseline urate was 331.4±83.8 and 302.7±78.0μmol/L for control and PD participants, respectively (p=0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μmol/L for controls and PD participants, respectively (p<0.01). Linear mixed effects modelling showed that lower baseline urate (β=0.02, p<0.001) and higher homocysteine (β=0.29, p<0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β=0.11, p<0.01). Conclusions: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.