Although we are breathing automatically in normal conditions, we can control breathing voluntarily for various purposes. It was shown by imaging studies that the human primary motor cortex (M1) is involved in the voluntary breathing, and that, within the M1, the activated areas are located adjacent to hand and forearm representations. Then, it is likely that excitability of the hand and forelimb areas in the M1 are modulated by breathing. Thus, we examined whether relatively weak voluntary control of respirations as oppose to automatic respirations probed by exhaled carbon dioxide (CO2) levels influence excitability of the primary motor cortex (M1) controlling the non-respiratory hand muscle, using transcranial magnetic stimulation (TMS) over the M1 of eight healthy human subjects. We applied TMS over the left M1 at inspiratory and expiratory phases of both normal breath and voluntary deep breaths in a self-paced manner while respiratory CO2 levels including end-tidal CO2 (ETCO2) were continuously monitored by a capnometer. Motor evoked potentials (MEP) were simultaneously recorded from five hand and forearm muscles: abductor pollicis brevis, first dorsal interosseous muscle, abductor digiti minimi, flexor digitorum superficialis, and extensor indicis of the right hand. We observed that MEP amplitudes of all the recorded muscle increased nearly 50% and their latencies decreased about 1 ms at low ETCO2 levels during deep breaths in comparison with those around 22 ms during normal breaths under higher ETCO2. There was no statistically significant difference in MEP amplitudes and latencies between stimulations at inspiratory and expiratory phases at the same CO2 levels during either normal or deep breaths. These results suggest that relatively weak voluntary drive on respiration system could enhance excitability of the M1 that controls the non-respiratory hand muscle through corticospinal pathway.