Cognitive abnormalities, including memory deficits, are common in heart failure (HF). Brain structures, including the hippocampus, fornix, and thalamus participate in memory processing, and most show structural injury and functional deficits in HF. The mammillary bodies and fornix play essential roles in spatial and working memory processing, interact with other structures, and may also be injured in HF. We assessed mammillary body volumes and cross-sectional fornix areas in 17 HF and 50 control subjects using high-resolution T1-weighted magnetic resonance images. Mammillary body volumes and fornix cross-sectional areas were significantly reduced bilaterally in HF, and these differences remained after controlling age, gender, and intracranial volume. Mammillary body and fornix injury may contribute to the compromised spatial and working memory deficits in HF. Pathological processes eliciting the damage may include injury accompanying hypoxic/ischemic processes in pathologic HF perfusion and breathing, and thiamine deficiency accompanying diuretic use and nutritional mal-absorption in the condition.