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INTRODUCTION Exposure to weightlessness induces a headward fluid shift and redistribution of fluids, resulting in increased internal jugular vein (IJV) cross-sectional area and altered IJV blood flow dynamics, including stasis and retrograde flow. These findings may contribute to various risks of spaceflight, including thrombosis or other risks affected by cerebral venous blood flow. To date, our understanding of the cerebral venous outflow dynamics in weightlessness is limited to the left IJV assessed ~45 and ~150 days into spaceflight. Therefore, it is unknown how quickly the alterations in venous blood flow dynamics change as a result of weightlessness. The purpose of this study is to determine 1) if venous stasis is an immediate effect of weightlessness and therefore a risk for short-duration missions and 2) the effect of weightlessness on brachiocephalic venous flow. METHODS In this study, we investigated the effects of acute weightlessness during parabolic flight on the right and left IJV in 12 healthy subjects. Baseline ultrasound images were obtained on the ground (1g) in the seated and supine postures and during 0g parabolic flight. Each data collection session included 2D ultrasonography to quantify IJV cross-sectional area and Doppler ultrasonography to characterize venous blood flow patterns in the bilateral IJVs. RESULTS There was a similar pattern of response in the left and right IJV area across postures and g-levels. IJV area increased from seated to supine by 0.74 mm2 (95% CI: 0.56 to 0.91 mm2, p<.001) and increased further during weightlessness by 0.29 mm2 (95% CI: 0.11 to 0.47 mm2, p=.0015). IJV Doppler images revealed stagnant flow in the left IJV in one subject during 0g exposure that was not present during any imaging on the ground; the right IJV continued to show pulsatile, nominal flow patterns in both 0g and 1g. CONCLUSIONS This study characterized the immediate effect of the weightlessness-induced headward fluid shift on venous parameters in the left and right IJV. The left IJV appears to be more susceptible to flow alterations, including stagnant flow, during both short and long-duration exposure to weightlessness that may contribute to the risk of thrombosis inflight.