Anesthetics induce a reversible coma-like state and alter the brain excitation. We showed that repeated exposure to ketamine causes the loss of the perineuronal nets (PNN) and reestablishes juvenile-like plasticity in the adult visual cortex (V1) (Venturino et al, 2021). Microglia enable the PNN dismantling and their depletion prevented this effect. In a side investigation, we observed that under acute ketamine exposure, microglia adapt in a sex-dependent manner. Thus, is there a sex-specific effect of how microglia modulate neuronal activity? Here, we show a sex-specific adaptation of the neuronal activity from single cell to brain networks connected to the microglial state. We performed in vivo electrophysiological recordings in V1 before and after anesthetic ketamine and identified sex-specific differences in gamma and beta-oscillations during the recovery phase. When we performed ex-vivo electrophysiological recordings of pyramidal neurons in V1, only females showed signs of meta-plasticity and spine formation, with increased microglia-pyramidal neuron interaction during in vivo live imaging. Microglia depletion prevented the plasticity remodeling. When we analyzed the microglia morphology across the cortical layers with morphOMICs (Colombo, Cubero et al, 2022), only female microglia responded in a defined morpho-phenotypical way. To identify a molecular signature of the female V1, we performed single-nuclei Multiome analysis and identified that ketamine has targeted effects on gene expression in microglia, astrocytes, and neuronal subpopulations. Remarkably, the same sexual-dimorphic microglia response occurred in acute human brain slices incubated with ketamine. Our results demonstrate that a sexual dimorphic microglia response exists that influences brain network activity.