The purpose of this study was to investigate muscle activity and endurance during fatiguing low-intensity dynamic knee extension exercise with and without blood flow restriction. Eleven healthy subjects with strength training experience performed 3 sets of unilateral knee extensions with no relaxation between repetitions to concentric torque failure at 30% of the 1 repetition maximum. One leg was randomized to exercise with cuff occlusion and the other leg to exercise without occlusion. The muscle activity in the quadriceps was recorded with electromyography (EMG). Ratings of perceived exertion (RPE) and acute pain were collected immediately, and delayed onset muscle soreness (DOMS) was rated before and at 24, 48, and 72 hours after exercise. The results demonstrated high EMG levels in both experimental conditions, but there were no significant differences regarding maximal muscle activity, except for a higher EMG in the eccentric phase in set 3 for the nonoccluded condition (p = 0.005). Significantly more repetitions were performed with the nonoccluded leg in every set (p < 0.05). The RPE and acute pain ratings were similar, but DOMS was higher in the nonoccluded leg (p < 0.05). We conclude that blood flow restriction during low-intensity dynamic knee extension decreases the endurance but does not increase the maximum muscle activity compared with training without restriction when both regimes are performed to failure. The high levels of muscle activity suggest that performing low-load dynamic knee extensions in a no-relaxation manner may be a useful method in knee rehabilitation settings when large forces are contraindicated. However, similarly to fatiguing blood flow restricted exercise, this method is associated with ischemic muscle pain, and thus its applications may be limited to highly motivated individuals.