Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily affecting females, characterised by the loss of motor skills and behavioural abnormalities linked to an excitatory/inhibitory imbalance involving GABA dysfunction. GABAergic deficits, particularly in somatostatin (SST) interneurons, play a crucial role in RTT pathophysiology and have been successfully replicated in mouse models. This study delves deeper into understanding the role of GABAergic interneuron inhibition in an RTT mouse model. Neonatal injections were administered to Mecp2tm1.1Bird x Sst-IRES-Cre mice at P1, followed by electrophysiological recordings from eGFP-expressing SST interneurons in the somatosensory cortex across layers 2/3 and 5 at P14, P21, P28, and P35. Six electrophysiological parameters, including resting membrane potential (RMP), action potential (AP) threshold, AP half-width, afterhyperpolarisation (AHP), and firing rate (FR), were meticulously recorded. A total of 29 SST interneurons were recorded from 11 different mice, with 24 meeting the criteria for further analysis.Significant differences in SST interneurons were observed in heterozygous Mecp2 mice compared to wild-type at P21, mainly in AP threshold (p = 0.009) and AHP (p = 0.041). Notably, no significant differences were identified between the cortical layers. Additionally, it is intriguing that heterozygous SST interneurons exhibited marginal variance compared to their wild-type counterparts.Although validation requires a larger sample size (N = 51, α = 0.80), GABAergic deficits in RTT likely stem from reduced synaptic activity at SST interneurons and other GABAergic interneurons rather than changes in their intrinsic properties. Further research will uncover specific neural connectivity and modulation, offering insights for potential therapies.