BACKGROUND: Sex and gender differences have been documented to influence cardiovascular diseases with an impact on disease management. Cadmium is a ubiquitous environmental toxicant that has been suggested to be a cardiovascular disease risk factor based on scientific evidence. This study investigated the gender difference in cardiotoxic and dyslipidemic effect associated with cadmium as there are dearth of scientific information in this regards. METHODS: Ten male and ten female Wistar rats (150-170g body weight) were fed with standard rat feed and water ad libitum under a condition of 12/12 hour light/dark cycle daily. The study was approved by the Bowen University Ethical committee with the number BUTH/REC-103. The rats were acclimatized for 7 days before subjecting them to different treatments and were treated for 21 days as follows (n=5): Control – Male; Cadmium chloride – Male (5mg/kg, p.o); Control – Female; Cadmium chloride – Female (5mg/kg, p.o). After the days of administration, rats were sacrificed by cervical dislocation under light ether. Blood and tissue samples were collected for estimation of tissue injury biomarkers, lipid peroxidation (MDA) and antioxidant, lipid profile and lipoprotein lipase according to standard laboratory procedures. Values are mean ± S.E.M, compared with ANOVA using Graph pad prism5. RESULTS: The results showed that creatinine kinase myocardial band (CK-Mb) and lactate dehydrogenase increased significantly in both gender as compared with their control (18.29 ± 2.5 vs 43.47 ± 1.2, p<0.001; 36.57 ± 8.012 vs 82.71 ± 10.72, p<0.05) . However, it increased significantly more in female than in male (43.47±1.2 vs 82.71 ± 10.72, P<0.05). Lipid peroxidation (MDA) increased in both gender but significantly in female compared with control (4.875 ± 0.07327 vs 6.176 ± 0.3531, P<0.05). Superoxide dismutase (SOD) reduced significantly in both treated groups compared with control (1.368 ± 0.07 vs 0.75 ± 0.06, P<0.0001; 1.15 ± 0.05 vs 0.75 ± 0.09, P<0.05) but no significant difference between male and female. No significant changes in catalase, glutathione and glutathione peroxidase. Total cholesterol increased in both male and female treated groups (110.6 ± 3.113 vs 138.2 ± 8.298, P<0.05; 124.7 ± 11.94 vs 162.4 ± 7.347, P=0.05). Although not significant, the value was higher in female than in male. Triglyceride increased significantly only in male compared with control (57.33 ± 1.704 vs 87.60 ± 11.45, P=0.05). There was no significant changes in low density lipoprotein across the groups, though the value increased in female by 17.8% compared with control (65.71 ± 7.874 vs 79.96 ± 5.553) and by 20.1% compared with male (63.82 ± 4.9 vs 79.96 ± 5.5). The high density lipoprotein and lipoprotein lipase increased significantly in the treated groups compared with their controls and not between male and female groups. CONCLUSION: Cadmium induced oxidative damage in the heart by enhancing membrane lipid peroxidation and also altered plasma lipid profile. Furthermore, the findings suggest that female gender is more susceptible than the male gender to cardiac oxidative stress and dyslipidemia associated with cadmium exposure.