Microglia, the tissue-resident macrophages of the central nervous system, actively participate in brain development by supporting neuronal maturation and refining synaptic connections. These cells are emerging as highly metabolically flexible, able to oxidize a variety of nutrients to meet their energy demand. Accumulating evidence points towards the involvement of metabolism and differential substrates catabolism in the regulation of immune cells. Lactate, which is abundant in the brain and sustains synaptic activity, also dictates responses of peripheral immune cells. However, the physiological role for lactate in modulating microglial function is still largely unexplored. Here we show that microglia can import lactate, which is converted into pyruvate and directly enters the TCA cycle. In parallel, lactate import in microglia induces increased lysosomal acidification and upregulation of the monocarboxylate transporter 4 (MCT4), a protein involved in lactate shuttles. In vitro, loss of MCT4 in microglia prevents lactate-induced lysosomal modulation and results in defective cargo phagocytosis. Microglia-specific depletion of MCT4 in vivo leads to impaired developmental synaptic pruning, associated with increased excitation in hippocampal neurons, enhanced AMPA/GABA ratio, vulnerability to kainic-acid induced seizures and anxiety-like phenotype.In summary, this study shows that lactate regulates important aspects of microglial physiology and that the selective disruption of the MCT4 transporter in microglia is sufficient to alter synapse refinement and to induce defects in brain development and adult behavior.