The leaves of the Xanthium spinosum plant have been used culturally in Paraguay for their medicinal properties. Acute toxicity of mature leaf extract was evaluated. For the study, 35 Balb/c mice were selected and allocated into 7 groups, 6 test groups and 1 control group. The extract was prepared in concentrations of 6% and 9% (g/dL). The 6% concentration was administrated to 3 test groups and 9% concentration to the remaining 3 groups, with doses between 200 and 1000 mg/kg per mouse. After 14 days of observation, blood samples were taken for laboratory studies of urea and transaminases and organs were examined for pathological studies. There were increased levels of GOT and urea in the test groups compared to the control group. In conclusion, the consumption of mature leaf extract of Xanthium spinosum can cause hepatic damage.