BACKGROUND: Injury prevalence data, muscle strength, and fatiguability differ between males and females. In addition, arm spatial orientation affects muscle activation and strength of the shoulder muscles. Nevertheless, little research has been conducted in relation to the shoulder rotator muscles comparing men and women. Therefore, the main aim of of this study was to perform a comparative investigation between two arm spatial orientations (45° and 90° of abduction in the frontal plane) during a fatigue assessment of the internal rotator (IR) and external rotator (ER) shoulder muscles. Secondly, the interaction between sex and dominance with muscular performance was assessed. METHODS: Forty healthy sedentary participants, 20 males and 20 females took part in this study. Participants performed a fatigue resistance protocol consisting of 30 consecutive maximal concentric contractions of the IR and ER shoulder muscles in a supine position at a speed of 180°/s. The upper limb was abducted to an angle of 45° or 90° in the frontal plane and each participant was tested on the dominant and nom-dominant side, counterbalanced in order of administration. Performance measures of Induced Fatigue (IF; %), Cumulated Performance (C.Perf; J) and Best Repetition (BR; J) were calculated and used for analysis. IF represents the % difference between the amount of work done over the last 3 and first 3 repetitions, BR represents the largest amount of work done during a single contraction, and C.Perf represents the total amount of work done during all repetitions. RESULTS: Muscle group was the only factor to display significant variation when not considering other factors, with higher values for C.Perf (mean difference = 353.59 J, P < 0.0005), BR (mean difference = 14.21 J, P < 0.0005) and IF (mean difference = 3.65%, P = 0.0046). There was a significant difference between both angles, with higher values observed at 90° compared to 45° of abduction for C.Perf by ~ 7.5% (mean difference = 75 to 152 J) and ~ 10.8% (mean difference = 5.1 to 9.4 J) for BR in the ER, in males and females respectively (P < 0.0005). The dominant arm was significantly stronger than the non-dominant arm for C.Perf by 11.7% (mean difference = 111.58 J) for males and by 18% (mean difference = 82.77 J) for females in the ER at 45° abduction. At 90° abduction, only females were stronger in the dominant arm by 18.8% (mean difference = 88.17 J). Values for BR ranged from 9.2 to 21.8% depending on the abduction angle and sex of the athlete (mean difference = 2.44 - 4.85 J). Males were significantly stronger than females by 48.8 to 50.7% for values of C.Perf and BR in both the IR and ER (P < 0.0005). There was a significant difference between the ER and IR muscles, with significantly higher values observed for the IR in C.Perf (mean difference = 331.74 J) by 30.0% and in BR (mean difference = 13.31 J) by 26.64%. DISCUSSION: Differences in shoulder performance fatiguability between sexes are affected by arm position, arm dominance and muscle groups. In agreement with the literature, performance values in males were approximately 50% higher than in females. However, the amount of IF was no different between both sexes. Based on findings in literature, it could be suggested that this is due to differences between males and females in motor control and/or coordination strategies during repetitive tasks. In addition, we also observed the IR muscles to be significantly stronger than the ER muscles. It has long been established in literature that these observations are due to the muscle-size differences between both muscle groups, where the IR muscles can produce a larger amount of force due to the larger cross-sectional area. Results of our study found similar ER:IR ratios compared to previous reports. CONCLUSION: Therefore, these findings are useful for clinicians when monitoring rehabilitation programs in sedentary individuals following shoulder injuries.