Exoskeletons have shown significant impact at reducing the biomechanical demand on muscles during repetitive lifting and overhead tasks in non-healthcare industries. However, the benefits of exoskeletons are yet to be realized in the operating room, particularly as work-related musculoskeletal disorders continue to be a concern for surgeons. This study quantified the effect of using neck, arm, and trunk exoskeletons on muscle activity while assuming typical postures held in the operating room. Fourteen participants were recruited to participate in this study. In this two-part experiment participants were asked to 1) hold a series of neck flexion, arm abduction and trunk flexion postures seen in surgical procedures, and 2) perform a simulated surgical task requiring five different trunk flexion posture levels. Participants were required to complete these tasks with and without passive exoskeleton(s). This study showed that even for postures held short time periods, exoskeletons are beneficial at reducing the demand on muscles; however, the reduction in muscle demand depends on body segment and postural angle, as intended with these passive exoskeletons. Furthermore, for the simulated surgical task with awkward trunk flexion postures (10–65°), the trunk exoskeletons showed a significant reduction in the rate of rise in back muscle sEMG (+1.365%MVC/min vs. +0.769%MVC/min for non-dominant lumbar extensor muscles, p = 0.0108; +1.377%MVC/min vs. +0.770%MVC/min for the dominant lumbar extensor muscles, p = 0.0196) over 25 min, consequently resulting in improved trunk subjective discomfort scores (7.34 vs. 4.30, p < 0.05), with no impact on the neck and shoulder biomechanical demand. The results from this study indicate that exoskeletons may be a potential intervention to reduce biomechanical loading during surgery.