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Highlights 1. There was no difference in the severity of chronic kidney disease (CKD) between male and female rats based on serum urea and creatinine levels as well as creatinine clearance. 2. As compared to females, males developed a more severe uremic cardiomyopathy characterized by left ventricular hypertrophy and fibrosis in CKD based on echocardiography and histology. 3. Following ischemia/reperfusion, infarct size was significantly smaller in females than in males, both in the sham-operated and CKD groups. 4. The infarct size-limiting effect of ischemic preconditioning (IPRE) was preserved in both sexes in CKD despite the more severe uremic cardiomyopathy in male CKD rats. 5. IPRE significantly increased the phospho-STAT3/STAT3 ratio in sham-operated, but not in CKD animals in both sexes.