There is conflicting evidence regarding the prevalence and magnitude of exercise-induced muscle damage (EIMD) following low-load resistance exercise with blood flow restriction (LL + BFR) that may be related to exercise protocols. The purpose of this investigation was to examine the effects of 75-repetition (BFR-75) (1 × 30, 3 × 15) and 4 sets to failure (BFR-4x) protocols on indices of EIMD among untrained women. Thirteen women completed this investigation. One leg was randomly assigned to BFR-75 and the other to BFR-4x. Each leg performed isokinetic, unilateral, concentric-eccentric, leg extension muscle actions at 30% of maximal strength. Indices of EIMD (muscle soreness, range of motion [ROM], limb circumference, pain pressure threshold [PPT], and maximal voluntary isometric contraction [MVIC]) were recorded before exercise, 0-, 24-, 48-, 72-, and 96-hours post-exercise. There were no changes for ROM, circumference, or PPT. Muscle soreness increased similarly in both conditions 0-, 24-, and 48-hours post-exercise and MVIC increased 24-, 48-, 72-, and 96-hours post-exercise. These findings suggested BFR-75 and BFR-4x were not associated with EIMD and elicited similar physiological responses. The increases in muscle soreness may be due to metabolic stress associated with LL + BFR protocols apart from EIMD.