In this study we investigated a technique for estimating the progression of localized muscle fatigue. This technique measures the dependence between motor units using high density surface electromyogram (HD-sEMG) and is based on the Normalized Mutual Information (NMI) measure. The NMI between every pair combination of the electrode array is computed to measure the interactions between electrodes. Participants in the experiment had an array of 64 electrodes (16 by 4) placed over the TA of their dominate leg such that the columns of the array ran parallel with the muscle fibers. The HD-sEMG was recorded whilst the participants maintained an isometric dorsiflexion with their dominate foot until task failure at 40% and 80% of their maximum voluntary contraction (MVC). The interactions between different locations over the muscle were computed using the recorded HD-sEMG signals. The results show that the average interactions between various locations over the TA significantly increased during fatigue at both levels of contraction. This can be attributed to the dependence in the motor units.