This study aims to determine the effect of body mass index (BMI), sleep patterns, working years, physical workload, mental workload, and work time on work fatigue on nurses at Hasanuddin University Hospital Makassar. This research is a quantitative study with a cross-sectional design with a sample size of 56 people. Sampling using a simple random sampling method. Data collection was carried out by means of a questionnaire. Bodyweight is measured by weight scales, body temperature is measured by microtoice, and physical workload is measured by a pulse oximeter, which is by looking at the pulse of the nurse before and after work. Data analysis in this study used the SPSS program. The results of this study indicate that there is an influence between Body Mass Index (BMI) on work fatigue (p = 0.001), there is an effect of sleep patterns on work fatigue (p = 0.019), there is an effect of tenure on work fatigue (p = 0.017), the relationship between physical workload and work fatigue (p = 0.000), there is an effect of mental workload on work fatigue (p = 0.000) and there is an effect of length of work on work fatigue (p = 0.017). The physical workload is the variable with the greatest influence on work fatigue on nurses at Hasanuddin University Hospital Makassar with Exp. (B) = 14,526. The results of this study concluded that there was a significant influence between the Body Mass Index (BMI), sleep patterns, years of work, physical workload, mental workload, and length of work for nurses at Hasanuddin University Hospital Makassar.