〔Abstract〕 To investigate the effect of Toxoplasma gondii infection on copper metabolism in the kidneys of mice. Methods A total of 80 7-8-week-old C57BL/6 female mice were randomly divided into four groups of 20 mice in each group after one week of adaptation, including Control group, Cu group, TgCtwh6 group and Cu+TgCtwh6 group. Mice that were not infected and fed with normal diet and water were used as the Control group; Mice fed with 1 g/kg of copper chloride processing diet and 0.1% copper chloride water for 60 consecutive days were used as Cu group; Mice infected with 25-30 TgCtwh6 cysts (one of the predominant genotype Chinese 1 in China) fed with normal diet and water were used as the TgCtwh6 group; mice infected with 25-30 TgCtwh6 cysts and fed with a processed diet containing 1 g/kg of copper chloride and water with 0.1% copper chloride for 60 consecutive days were used as the Cu+TgCtwh6 group. ICP-MS was used to determine the changes in copper content in kidney tissues. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of mouse kidney tissue. The number of apoptotic cells was observed by PI staining. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD1, SOD2).RT-qPCR was used to detect the mRNA expression of cuproptosis-related genes. Results Pathological manifestations such as inflammatory cell infiltration in the Cu group and TgCtwh6 group were seen under the microscope, and the inflammatory infiltrating cells of the renal interstitial were reduced in the Cu+TgCtwh6 group, and the pathological manifestations of glomerular tubular structure were improved. The number of apoptotic cells in the Cu+TgCtwh6 group (88.36±19) was lower than that in the Cu group (119.0±20). Compared with the Cu+TgCtwh6 group, the expression of SOD1 protein was down-regulated, and the difference was statistically significant (P<0.05). TgCtwh6 infection could restore the down-regulation of renal GLS expression and the up-regulation of ATP7B expression caused by copper overload. Conclusion Toxoplasma gondii infection can interfere with the copper metabolism pathway in the kidney of mice, improve the kidney damage caused by copper overload, and provide new clues for the treatment of copper overload disease.