The aim of this study was to quantitatively analyze the mechanical change of spinal segments (disc, muscle, and ligament) at various postures under microgravity using a full-body musculoskeletal modeling approach. Specifically, in the lumbar spine, the vertebra were modeled as rigid bodies, the intervertebral discs were modeled as 6-degree-of-freedom joints with linear force-deformation relationships, the disc swelling pressure was deformation dependent, the ligaments were modeled as piecewise linear elastic materials, the muscle strength was dependent on its functional cross-sectional area. The neutral posture and the "fetal tuck" posture in microgravity (short as "Neutral 0G" and "Fetal Tuck 0G", in our simulation, the G constant was set to 0 for simulating microgravity), and for comparison, the relaxed standing posture in 1G and 0G gravity (short as "Neutral 1G" and "Standing 0G") were simulated. Compared to values at Neutral 1G, the mechanical response in the lower spine changed significantly at Neutral 0G. For example, the compressive forces on lumbar discs decreased 62-70%, the muscle forces decreased 55.7-92.9%, while disc water content increased 7.0-10.2%, disc height increased 2.1-3.0%, disc volume increased 6.4-9.3%, and ligament forces increased 59.5-271.3% at Neutral 0G. The fetal tuck 0G reversed these changes at Neutral 0G back toward values at Neutral 1G, with magnitudes much larger than those at Neutral 1G. Our results suggest that microgravity has significant influences on spinal biomechanics, alteration of which may increase the risks of disc herniation and degeneration, muscle atrophy, and/or ligament failure.