Recent studies are elucidating the interrelation between sleep, cranial perfusion, and cerebrospinal fluid (CSF) circulation. Head down tilt (HDT) as a simulation of microgravity reduces cranial perfusion. Therefore, our aim was to assess whether HDT is affecting sleep (clinicaltrials.gov; identifier NCT02976168). 11 male subjects were recruited for a cross-over designed study. Each subject participated in two campaigns each comprising 3 days and 2 nights. Intervention started on the second campaign day and consisted of maintenance of horizontal position or -12° HDT for 21 h. Ultrasound measurements were performed before, at the beginning and the end of intervention. Polysomnographic measurements were assessed in the second night which was either spent in horizontal posture or at -12° HDT. Endpoints were sleep efficiency, sleep onset latency, number of sleep state changes and arousals, percentages of N3, REM, light sleep stages and subjective sleep parameters. N3 and REM sleep reduced by 25.6 and 19.1 min, respectively (P = 0.002, g = -0.898; P = 0.035, g = -0.634) during -12° HDT. Light sleep (N1/2) increased by 33.0 min at -12° HDT (P = 0.002, g = 1.078). On a scale from 1 to 9 subjective sleep quality deteriorated by 1.3 points during -12° HDT (P = 0.047, g = -0.968). Ultrasonic measurement of the venous system showed a significant increase of the minimum (P = 0.009, P < 0.001) and maximum (P = 0.004, P = 0.002) cross-sectional area of the internal jugular vein at -12° HDT. The minimum cross-sectional area of the external jugular vein differed significantly between conditions over time (P = 0.001) whereas frontal skin tissue thickness was not significantly different between conditions (P = 0.077, P = 0.811). Data suggests venous congestion at -12° HDT. Since subjects felt comfortable with lying in -12° HDT under our experimental conditions, this posture only moderately deteriorates sleep. Obviously, the human body can almost compensate the several fold effects of gravity in HDT posture like an affected CSF circulation, airway obstruction, unusual patterns of propioception and effects on the cardiovascular system.