The purpose was to investigate muscle activation during low- intensity muscle contractions with various levels of external limb compression to reduce muscle perfusion/outflow. A series of unilateral elbow flexion muscle contractions (30 repetitive contractions followed by 3 sets x 15 contractions) was performed at 20% of 1RM with varying levels of external compression (0 (without compression), 98, 121, and 147 mmHg external compression) around the upper arm. Electromyography (EMG) signals were recorded from surface electrodes placed on the biceps brachii muscle and analyzed for integrated EMG (iEMG). Maximal voluntary isometric contraction (MVC) decreased similarly during the control (0 mmHg) and 98 mmHg external compression bout (~18%); the decline in MVC with 121 and 147 mmHg external compression was significantly greater (~37%). Muscle activation increased progressively throughout the contraction bout with each level of external compression, but iEMG was significantly greater during 147 mmHg external compression. In conclusion, low-intensity muscle contractions performed with external compression of 147 mmHg appears to alter muscle perfusion/outflow leading to increased muscle activation without decrements in work performed during the contraction bout. Key pointsLow-intensity muscle contractions with external compression are maintained by greater neural activation.It appears there is optimal external compression pressure for increased muscle activation without exaggerated fatigue.External compression per arm circumference was related to the neuromuscular response and fatigue.