Purpose <p>It is unclear if corticospinal excitability and inhibition differ between healthy, young males and females, and between muscles of the upper and lower limb. The purposes of this study were to identify sex- and muscle-related differences in corticospinal excitability and inhibition.</p> Methods <p>Twenty healthy males (age: 23.2 ± 2.7 years) and 20 healthy females (age: 22.7 ± 2.2 years) participated in this study. Transcranial magnetic stimulation was used to elicit motor evoked potentials (MEP) and corticospinal silent periods (CSP) from the first dorsal interosseous and tibialis anterior muscle during a contraction to assess corticospinal excitability and inhibition.</p> Results <p>Motor evoked potential amplitude was similar between males and females (<i>p</i> = 0.66) and between muscles of the upper and lower limb (<i>p</i> = 0.19). Corticospinal silent period duration was significantly longer in males than females in both muscles (<i>p</i> &lt; 0.01) with no significant differences between muscles (<i>p</i> = 0.74).</p> Conclusion <p>These results suggest that males may have greater corticospinal inhibition than females in muscles of both the upper and lower limb, despite, similar excitability.</p>