Chromolaena odorata is a medicinal plant widely used in traditional medicine, despite its therapeutic applications, there are concerns regarding its potential toxic effects. This study investigates the dose-dependent effects C odorata on male fertility of adult male Wistar. A total of 25 male rats were randomly assigned into 5 groups (n = 5). Group A (Control), received distilled water, while groups B, C, D, and E were administered 120, 200, 500, and 700 mg/kg of the aqueous extract of C. odorata daily for 28 days respectively, after which they were sacrificed. Testicular weights, hormone levels, total protein, and oxidative stress markers were evaluated, and the testis evaluated histologically. GraphPad Prism Version 10.2 was used to analyse the data. Results were described as mean ± Standard Error of Means (S.E.M.). An unpaired t-test (at a 95% confidence level) was used to compare the values of the control and experimental groups.There was a statistically significant reduction (P <
0.05) in testicular weights, hormone levels (LH, FSH, Testos,), total protein concentration and a significant increase in catalase and malondialdehyde in groups D and E. Histomorphological analysis of groups D and E revealed severe structural distortions in the testis, presence of inflammatory cells, collapsed lumen with reduced luminal content, degenerating epithelium, loss of stereocilia cells, and poorly arranged connective tissue fibers. High-dose administration of C. odorata extract induces significant histomorphological damage to the testis, disrupts reproductive hormone levels, and increases oxidative stress, resulting in impaired male fertility in Wistar rats.