Microglia are keen responders in numerous neurodevelopmental and neurodegenerative conditions, including in Multiple Sclerosis (MS). While previous studies hinted about microglia involvement in synaptic elimination, their correlation with the appearance of cognitive deficits in MS remains unclear. Here, we focused on understanding the impact of microglia in MS synapse pruning in the cognitive-related region, the hippocampus, using postmortem tissue of MS patients. Hippocampal samples were obtained from the Netherlands Brain Bank, including non-demented control (NDC) and MS donors that were matched for age and postmortem delay. According to clinical neuropsychological data, MS patients were categorized based on cognitive status: preserved (MSCP) and impaired cognition (MSCI). Immunohistochemistry studies explored microglia (Iba1), their interaction with immune cells (CD8 T-cells), and their role in synapse (vGat/vGlut1) engulfment. In hippocampal lesions, MSCI patients exhibited a significant infiltration of microglia (*p<0.05 vsNDC; #p<0.05 vs MSCP), accompanied by alterations in cell area and volume. Additionally, we found an increased density of CD8 T-cells particularly in MSCI patients (**p<0.01 vs NDC; ##p<0.01 vs MSCP), in close proximity to microglia (~35%). When evaluating high synaptic density hippocampal regions, we detected a pronounced presence of microglia in MSCI patients, actively engulfing both excitatory and inhibitory synapses in MSCI patients (*p<0.05 vs NDC; #p<0.05 vs MSCP for vGlut; *p<0.05 vs NDC for vGat). In summary, our findings confirmed that microglia play a pivotal role in the mechanisms underlying cognitive deficits in MS.