Peripartum cardiomyopathy (PPCM) is a rare but devastating cardiac failure of indeterminate etiology occurring in late pregnancy or early puerperium. The prevalence of PPCM in Northern Nigeria could be attributed to the unique customary puerperal practices of prolonged consumption oflarge quantities of Guiera senegalensis and Natron. This study investigated the effect of decoction of G. senegalensis with and without Natron on cardiac markers, lipid profile and histology ofheart in postpartum female albino rats using standard methods.Thirty-five (35)female albino rats of body weights 190-200 g of five month were randomly grouped into seven (7) of five rats each. Group 2, 3 and 4 were orally administered with 100, 200 and 300 mg/kg body weight of G. senegalensis. Group 5, 6 and 7 were orally administered with 100, 200 and 300 mg/kg body weight (1:1) of G. senegalensis and Natron by gavage, whereas group 1 received distilled water. The study revealed significant (p< 0.05) decrease in triglyceride(TG) in group 2 to VII, high density lipoproteincholesterol (HDL-c) in group 2, 5 and 6, very low density lipoprotein- cholesterol (VLDL-c) in group 3 to V, couples with significant (p< 0.05) increase in low density lipoprotein cholesterol (LDL-c) in group 2, 3, 5 and 7, and for (AIX) in group 2, total cholesterol(TC) in group 2, 3 and 7 when compared with control. Significant (p< 0.05) increase in Lactate dehydrogenase (LDH) in group 3 to 7, and Myoglobin (MB) in group 3 was observed. Significant (p< 0.05) decrease in Troponin I (TnI) in group 2 and 4 was seen. There were no significant (p>0.05) changes in Troponin T (Tn T), aspartate amino transferase (AST) and Creatine Kinase(CK-NAC) of the treatment group when compared to control group. Histopathological examination of section of the heart revealed ventricular dilatation, hypertrophied with enlarged nuclei, stretched, and irregular and mural thrombi in group 2 to 4 and 7. Inflammation in group 5 and 7, Pigment deposited in group 4 to 7 and Mild fibrosis in group 3 were observed. The study demonstrates that consumption of G. senegalensis and Natron for 28 days’induces dyslipidemia and causes changes in the heart of postpartum rats and thus may contribute to the pathogenesis of PPCM.