REASONS FOR PERFORMING STUDY: The aetiopathogenesis of equine grass sickness (EGS) is unknown. The role of free radical-mediated neuronal damage has not previously been investigated in this condition. OBJECTIVES: To investigate the potential contribution of oxidative damage and antioxidant status to neurodegeneration in EGS. METHODS: Systemic levels of surrogate biomarkers were determined in 10 horses with acute EGS and in 2 control populations; 10 healthy horses co-grazing with the 10 EGS horses at the onset of clinical disease, and 10 healthy mares grazing where EGS has not been reported. RESULTS: EGS horses had alterations in levels of several antioxidants, consistent with oxidative stress, the acute phase response and/or the secondary metabolic complications of EGS. EGS horses had elevated plasma dihydroxyphenylalanine (DOPA) levels. CONCLUSIONS: The elevated DOPA levels probably reflected a generalised disturbance of catecholamine metabolism rather than increased DOPA production via free radical-mediated oxidation of tyrosine. However, there was no evidence of systemic macromolecular oxidative damage. POTENTIAL CLINICAL RELEVANCE: Further work is required to determine whether macromolecular oxidative damage occurring at the neuronal level contributes to EGS.