The purpose of this study was to determine the effect of three different back squat protocols on intra-cellular signaling, endocrine responses, and power fatigue. Nine recreationally trained males (X±SD; age: 21.4±0.6yrs; height: 177.8±5.1cm; weight: 78.7±9.7kg), completed three maximal concentric velocity squat protocols in a randomized order. Testing protocols consisted of 5 sets of 10 repetitions at 30% of 1RM; 5 sets of 5 repetitions at 70% of 1RM; and 5 sets of 3 repetitions at 90% of 1RM. Average system power for each set was obtained with a tethered external dynamometer. Pre- and post-exercise blood draws were analyzed for lactate, testosterone, hGH, and cortisol. Muscle biopsies assessed pre- and post-exercise extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 phosphorylation via western blotting. Cortisol, hGH, and lactate increased post-exercise (p<0.05), but did not differ between protocols (p>0.05). Testosterone was unaltered (p>0.05). Average power was lower for the 90% protocol than for the 30% protocol across all sets (p<0.01). Average power was lower after the fourth and fifth set compared to the first and second set in the 90% protocol only (p<0.05). The ratio of phosphorylated-to-total ERK1/2 was higher post-exercise after 90% protocol only (p<0.05). The ratio of phosphorylated-to-total p38 was unaltered post-exercise (p>0.05). Resistance load appears to affect power fatigue across the five sets of resistance exercise. This study found modest changes in ERK1/2 and no changes in p38 phosphorylation following maximal concentric velocity squats. Exercise volume, modality, and training status of subjects may account for these findings.