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Background: The condition of fatigue is a complex and multifaceted disorder that encompasses physical, mental, and psychological dimensions, all of which contribute to a decreased quality of life. Smartphone-based systems are gaining significant research interest due to their potential to provide noninvasive monitoring and diagnosis of diseases., Objective: This paper studies the feasibility of using smartphones to collect motor skill related data for machine learning based fatigue detection. The authors' main goal is to provide valuable insights into the nature of fatigue and support the development of more effective interventions to manage it., Methods: An application for smartphones running on Android OS is developed. Two aim-based reaction tests, an Archimedean spiral test, and a tremor test, were assembled. 41 subjects participated in the study. The resulting dataset consists of 131 trials of fatigue assessment alongside digital signals extracted from the motor skill tests. Six machine learning classifiers were trained on computed features extracted from the collected digital signals., Results: The collected dataset SmartPhoneFatigue is presented for further research. The real-world utility of this database was shown by creating a methodology to construct a fatigue predictive model. Our approach incorporated 60 distinct features, such as kinematic, angular, aim-based, and tremor-related measures. The machine learning models exhibited a high degree of prediction rate for fatigue state, with an accuracy exceeding 70%, sensitivity surpassing 90%, and an f1-score greater than 80%., Conclusion: The results demonstrate that the proposed smartphone-based system is suitable for motion data acquisition in non-controlled environments and shows promise as a more objective and convenient method for measuring fatigue., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)