Sympathetic activity is increased during late-expiratory (late-E) phase in chronic intermittent hypoxic (CIH) rats. We evaluated the mechanisms involved in the CIH-induced changes in electrophysiological properties of medullary respiratory and pre-sympathetic neurons. At 11th day after CIH, the rats were deeply anesthetized with halothane and decerabrated and then placed in the recording chamber for in in situ working heart brainstem preparation of wistar rats. We performed simultaneous recordings of respiratory and sympathetic nerves with intracellular or whole cell path-clamp of respiratory and pre-sympathetic neurons of ventrolateral medulla. In CIH rats, the decrease in the frequency discharge of Bötzinger post-inspiratory [post-I, (n=28)] neurons reduced the post-I activity of cervical vagus nerve (n=10). The overactivities of augmenting expiratory [aug-E, (n=55)] and pre-Bötzinger pre-inspiratory [pre-I, (n=30)] neurons increased the late-E abdominal (n=28) and pre-I hypoglossal (n=20) nerves activities. Due to this changes, the frequency discharge of pre-sympathetic neurons (n=27) and thoracic sympathetic activity (n=30) were enhanced time-locked with AbN late-E activity. However, CIH produced changes in the input resistance and excitability, independent of synaptic transmission, only in the pre-I (179±13 vs 253±22 MΩ; 25±3 vs 47±2 pA; p<0.05; n=15) and post-I neurons (355±15 vs 250±31 MΩ; 71±3 vs 51±2 pA; p<0.05; n=17). These changes were accompanied by increase in the inward riluzole-sensitive persistent sodium current (at -50 mV: 156 ± 15 vs 72 ± 20 pA, p<0.05; n=6) and in the 4-aminopyridine-sensitive component of transient outward potassium current (at 60 mV: 405 ± 75 vs 210 ± 77 pA; p<0.05; n=9) in the CIH pre-I and post-I neurons, respectively. These data describe novel mechanisms underlying sympathetic overactivity, which critically depend on changes of ionic currents of medullary respiratory neurons of CIH rats.