Cardiovascular autonomic modulation during 36 hours of total sleep deprivation (SD) was assessed in 18 normal subjects (16 male, 2 female, 26.0 ± 4.6 yrs). ECG and continuous blood pressure (BP) from radial artery tonometry were obtained at 2100 hrs on the first study night (baseline), and every subsequent 12 hours of SD. Each measurement period included resting supine, seated, and seated performing computerized tasks measuring vigilance and executive function. Subjects were not supine in the periods between measurements. Spectral analysis of heart rate variability (HRV) and BP variability (BPV) was computed for cardiac parasympathetic modulation (high frequency power, HF); sympathetic modulation (low frequency power, LF), sympatho-vagal balance (LF/HF power of R-R variability, LF_R-R/HF_R-R) and BPV sympathetic modulation (low frequency power, BPV LF). All spectral data were expressed in normalized (n) units ([total power of the components]/[total power-very low frequency power] x 100). Spontaneous baroreflex sensitivity (BRS), based on systolic BP and pulse interval powers, was also measured. Supine and sitting, BPV LF (n) was significantly increased from baseline at 12, 24, and 36 hours of SD. Sitting, HRV LF (n) was increased at 12 and 24 hours SD, HRV HF (n) was decreased at 12 hours SD, and HRV LF_RR/ HF_R-R was increased at 12 hours SD. BRS was decreased at 24 hours SD supine and seated. During the simple reaction time task (vigilance testing), the significantly increased sympathetic and decreased parasympathetic cardiac modulation and BRS extended through 36 hours SD. In summary, acute SD was associated with increased sympathetic and decreased parasympathetic cardiovascular modulation and decreased baroreflex sensitivity, most consistently in the seated position and during simple reaction time testing.