Simple SummaryOxidative stress is an adverse condition in animals that can cause tissue damage and result in poor health. A number of factors can contribute to this condition, although little has been studied empirically in elephants. This study measured multiple serum oxidative status markers and a stress biomarker (fecal glucocorticoid metabolites) to examine the effects of age, sex, sampling season, and disease factors in captive Asian elephants in Thailand. Age and season influenced several biomarkers and should be considered in data interpretation, while sex did not. The most significant changes in oxidative and antioxidative activity were associated with elephant endotheliotropic herpesvirus hemorrhagic disease, a highly fatal disease in calves, suggesting a strong link with oxidative stress responses.AbstractOxidative stress is a pathological condition that can have adverse effects on animal health, although little research has been conducted on wildlife species. In this study, blood was collected from captive Asian elephants for the assessment of five serum oxidative status markers (reactive oxygen species (ROS) concentrations; malondialdehyde, MDA; albumin; glutathione peroxidase, GPx; and catalase) in healthy (n= 137) and sick (n= 20) animals. Health problems consisted of weakness, puncture wounds, gastrointestinal distress, eye and musculoskeletal problems, and elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD). Fecal samples were also collected to assess glucocorticoid metabolites (fGCMs) as a measure of stress. All data were analyzed in relation to age, sex, sampling season, and their interactions using generalized linear models, and a correlation matrix was constructed. ROS and serum albumin concentrations exhibited the highest concentrations in aged elephants (>45 years). No sex differences were found for any biomarker. Interactions were observed for age groups and seasons for ROS and catalase, while GPx displayed a significant interaction between sex and season. In pairwise comparisons, significant increases in ROS and catalase were observed in summer, with higher ROS concentrations observed only in the adult female group. Lower catalase activity was exhibited in juvenile males, subadult males, adult females, and aged females compared to subadult and adult elephants (males and females) in winter and the rainy season. There was a positive association between catalase activity and fGCMs (r = 0.23,p< 0.05), and a number of red blood cell parameters were positively associated with several of these biomarkers, suggesting high oxidative and antioxidative activity covary in red cells (p< 0.05). According to health status, elephants with EEHV-HD showed the most significant changes in oxidative stress markers, with MDA, GPx, and catalase being higher and albumin being lower than in healthy elephants. This study provides an analysis of understudied health biomarkers in Asian elephants, which can be used as additional tools for assessing the health condition of this species and suggests age and season may be important factors in data interpretation.