The entorhinal cortex (EC) is important for learning and memory. Our laboratory recently identified a sex difference in the excitability of neurons within the sixth EC layer (ECVI) during early postnatal life, in that neurons from female mice are more excitable than neurons from male mice. While this sex difference correlates with a smaller afterhyperpolarization of medium duration (mAHP) in female ECVI neurons, its precise mechanisms have not been determined. Using whole-cell electrophysiology, this study aims to determine the contribution of small-conductance calcium-activated potassium (SK) channels toward ECVI neuron excitability in young postnatal (P5-10) and adult (P80-120) mice. Our findings demonstrate that SK channels do not regulate ECVI neuronal excitability in early postnatal life but do regulate excitability in adulthood. In adulthood, SK channels play a greater role in regulating ECVI neuron excitability in male mice than in female mice. This knowledge advances our understanding of neuron function within the hippocampal formation.