Sleep deprivation, resulting from factors such as lifestyle, disease, or environmental influences, directly contributes to cognitive decline. Research has found that the impact of sleep deprivation on microglia may be a key factor in cognitive impairment. The specific mechanisms through which microglia contribute to this process are not yet fully understood. It may act through multiple pathways, including the accumulation of excitatory neurotransmitters, A beta plaque deposition, neuroinflammation, disrupted autophagy, abnormal cell death, and impaired synaptic plasticity. This review synthesizes evidence from the past two decades on the interplay between microglia, sleep deprivation, and cognitive impairment. It provides a comprehensive overview of associated factors and their operational pathways, analyzes the network of pathological interactions, and identifies possible treatment directions. It also emphasizes the dual functions of microglia in worsening and alleviating cognitive impairment while investigating possible therapeutic strategies targeting microglial function. This review aims to clarify microglial pathways in sleep-loss-related cognitive deficits, thereby advancing the field and providing a foundation for new therapeutic strategies.