Overhead work activities can lead to shoulder pain and serious musculoskeletal disorders (WMSD), such as rotator cuff injury and degeneration. Recently developed exoskeletons show promising results in supporting workers in such activities. In this study, a novel exoskeleton was investigated for two different overhead tasks with twelve participants. To investigate the effects of the device, electromyographic (EMG) signals of different shoulder and adjacent muscles as well as kinematic and metabolic parameters were analyzed with and without the exoskeleton. The mean EMG amplitude of all evaluated muscles was significantly reduced when the exoskeleton was used for the overhead tasks. This was accompanied by a reduction in both heart rate and oxygen rate. The kinematic analysis revealed small changes in the joint positions during the tasks. This study demonstrated the biomechanical and metabolic benefits of an exoskeleton designed to support overhead work activities. The results suggest improved physiological conditions and an unloading effect on the shoulder joint and muscles which are promising indicators that the exoskeleton may be a good solution to reduce shoulder WMSD among workers who carry out overhead tasks on a regular basis.