Abstract Background context There is conflicting evidence regarding erector spinae muscle fatigability because previous studies have not considered the thoracic and lumbar components separately. These muscles have very different mechanical responses and, therefore, would be recruited differentially for the chosen task. Purpose The present study was conducted to compare whether fatigability differences exist in the thoracic and lumbar parts of the erector spinae muscles in subjects with and without low back pain (LBP). Study design This cross-sectional study was conducted in the Motion Analysis Lab at Cleveland State University. Patient sample The study sample included 40 subjects with LBP and 40 subjects without LBP. Outcome measures The fatigability of the erector spinae muscles was compared based on median frequency of electromyography (EMG) versus time. The level of pain of each subject was also compared using the Oswestry Disability Index. Methods Fatigue measurements were evaluated between groups based on the assessed sides as well as the thoracic and lumbar parts of the erector spinae muscles using surface EMG. A modified version of the isometric fatigue test as introduced by Sorensen was used to test the endurance of the erector spinae muscles. Results There were significant median EMG frequency (F (1, 78)=28.82, p=.001) differences in the thoracic and lumbar parts of the erector spinae muscles between subjects with and without LBP. The thoracic part had a significantly lower median EMG frequency than the lumbar part in subjects with LBP. The thoracic and lumbar parts of the erector spinae muscles had interactions with group (F (1, 78)=47.88, p=.01] and age (F (1, 78)=16.51, p=.01). Conclusions The results of this study suggested that subjects with LBP demonstrated higher fatigability of the erector spinae muscles at the thoracic part than at the lumbar part. The increased fatigability of the thoracic part needs to be emphasized in rehabilitation strategies for subjects with LBP. In addition, as age increased, the median frequency of the lumbar part of the erector spinae muscles significantly decreased. Understanding the anatomical and biomechanical characteristics of the erector spinae muscle may enhance clinical outcomes and rehabilitation strategies for subjects with LBP.