Cardiometabolic disease is associated with energy dysregulation. Short chain fatty acids have shown potential to improve insulin resistance-associated disturbances. We hypothesize that acetate would enhance key cardiac metabolism enzymes in combined oral contraceptive (COC)-treated dams with insulin resistance. Female rats (130-150g) were mated to achieve timed pregnancy and delivery. Ttwenty-four (24) dams were randomly grouped into vehicle (p.o), fructose exposed dam (FDAM), FDAM + COC, FDAM + acetate (ACE) and FDAM + COC + ACE groups (6rats/group). The groups received distilled water (vehicle, p.o.), 10% Fructose (w/v) , 10% Fructose plus 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel (p.o.), and 10% Fructose plus COC + ACE [200mg/kg bw (p.o.)] respectively. Pregnant rats were exposed to fructose drink daily for 19 days. After weaning, dams received COC 3rd and 6th weeks postpartum. After anaesthetisia with pentobarbital sodium (50 mg/kg, ip), blood sample was collected via cardiac puncture and cardiac tissue was harvested for biochemical assays. The Use of Laboratory Animals and was approved by the Institutional Ethical Review Board of University of Ilorin. All data were expressed as means ± SEM and significance were accepted at p<0.05 and n=6. Data show that postpartum COC administration in fructose-exposed dams worsened insulin resistance, plasma and cardiac lipid deposition, hyperuricemia. IR phenotype in this model is accompanied with decreased high density lipoprotein-cholesterol level, pyruvate dehydrogenase and aconitase activities in the heart. However, supplementation with acetate improved insulin resistance-related disturbances and enhanced cardiac pyruvate dehydrogenase and aconitase activities in COC-treated dams with insulin resistance. Our findings suggest that cardiac dysfunction caused by postpartum COC treatment in fructose-exposed insulin-resistant dams is associated with dyslipidemia, cardiolipotoxicity and impaired key mitochondrial enzymes in the heart. Acetate supplementation however shows plausible ameliorative potential against postgestational COC-worsened IR-related cardiac dysfunction.