Cognitive dysfunction induced by sepsis is a common clinical disease. The hippocampus is one of the brain regions most vulnerable to sepsis. However, the correlations between sepsis-mediated neural cell types, pathological characteristics, and molecular mechanisms in hippocampal tissue and brain cognitive damage remain incompletely understood. This review summarizes: (1) the pathological features and mechanisms of blood-brain barrier disruption in sepsis; (2) the pathological effects of sepsis on different types of hippocampal neurons and the underlying molecular mechanisms; (3) the activation of peripheral inflammatory cells and central resident microglia and their roles in neuronal and oligodendrocyte death, as well as synaptic pruning, along with the associated mechanisms; and (4) the activation of sepsis-induced reactive astrocytes and their impact on cognitive function. Finally, this article analyzes potential therapeutic strategies for sepsis-associated brain cognitive dysfunction.