Mutations in the X-chromosome gene PCDH19 cause Developmental and Epileptic Encephalopathy-9 (DEE9), a rare neurodevelopmental disorder characterized by epilepsy, autism spectrum disorder and cognitive impairment. DEE9 is characterized by a peculiar gender preference, affecting mainly heterozygous females.Recently, it was found that in vivo mosaic expression of Pcdh19 impairs the maturation and migration of neurons and the GABAergic circuitry, leading to defects of excitation/inhibition (E/I) balance. Since the GABAergic parvalbumin interneurons (PVIs) are powerful regulators of pyramidal neuron activity and alteration in their function is deeply related to epilepsy and neurodevelopmental disorders, we generated a novel conditional PV-Cre/Pcdh19 KO mice (cKO) to study the functional consequences of the selective loss of Pcdh19 in PVIs. PV-Cre/Pcdh19 mice displayed defects in sociability, suggestive of an autistic-like behavior. Interestingly, the characterization of the electroencephalographic profile of cKO mice showed a dysfunctional cortical excitability and a strong epileptic susceptibility. Remarkably, pyramidal neurons had a more excitable phenotype, while PVIs were unaltered. Finally, by recording calcium transients using in vivo single cell microendoscopic Ca2+ imaging during social exploration, we showed an altered pattern of activation of single PVIs of prefrontal cortex in response to the interaction stimulus.Altogether these results indicate that the selective deletion of Pcdh19 in PVIs affects social motivation and cortical excitability, suggesting that PVI excitability may contribute to the symptomatology associated with DEE9.