Mine workers in South Africa face challenges relating to poor health and safety, including fatigue risks, and poor socioeconomic and living conditions. Fatigue results in impaired mental and physical performance. The aim of this study was to assess contributors to fatigue of mine workers in South Africa.Data collection took place at four gold mines and one platinum mine in South Africa. A total of 21 focus groups were held with individuals in management, union representatives, and mine workers, and 564 questionnaires were completed by mine workers to gather information about fatigue and potential contributors to fatigue at these mines.Qualitatively (through focus groups), fatigue was attributed to extended working hours, harsh working conditions, high workloads, production pressure, and resource constraints, along with aspects relating to demographic and socioeconomic factors, living conditions, lifestyle, health, and wellness. Greater fatigue was significantly associated with younger age, indebtedness, a lack of exercise, poor nutrition, less sleep, increased alcohol use, poor self-reported health, more sick leave, higher stress, and lower job satisfaction.The aim of the study was achieved; numerous work-, sociodemographic-, lifestyle-, and wellness-related factors were linked to fatigue in the participating mine workers. Contributors to fatigue should be addressed to improve health, safety, and sustainability in the industry.