Repetitive electrically-evoked muscle contraction leads to accelerated muscle fatigue. This study assessed electrically-evoked fatiguing muscle with changes to mechanomyography root mean square percentage (%RMS-MMG) and tissue saturation index (%TSI) in extensor carpi radialis. Forty healthy volunteers (n=40) performed repetitive electrical-evoked wrist extension to fatigue and results were analyzed pre- and post-fatigue, i.e. 50% power output (%PO) drop. Responses of %PO, %TSI and %RMS-MMG were correlated while the relationships between %RMS-MMG and %TSI were investigated using linear regression. The %TSI for both groups were negatively correlated with declining %PO as the ability of the muscle to take up oxygen became limited due to fatigued muscle. The %RMS-MMG behaved in two different patterns post-fatigue against declining %PO whereby; (i) group A showed positive correlation (%RMS-MMG decreased) throughout the session and (ii) group B demonstrated negative correlation (%RMS-MMG increased) with declining %PO until the end of the session. Regression analysis showed %TSI was inversely proportional to %RMS-MMG during post-fatigue in group A. Small gradients in both groups suggested that %TSI was not sensitive to the changes in %RMS-MMG and they were mutually exclusive. Most correlation and regression changed significantly post-fatigue indicating that after fatigue, the condition of muscle had changed mechanically and physiologically.