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Despite all the positive effects of cell phones on communication, the improper use of these devices may lead to fatigue and many other problems, including academic, physical, and social problems. Among different age groups, students are the most affected due to the importance of cell phones in their educational and communications needs. In this study, we seek to investigate the relationship between improper use of cell phones and fatigue in Iranian medical students. In the present descriptive-analytical and cross-sectional study, 400 students were randomly selected from the Iran University of Medical Sciences by cluster sampling. Data collection tools included demographic information questionnaires, harmful cell phone use (COS), and fatigue (Smets). Data were analyzed using SPSS software version 22 based on the frequency tests, mean, standard deviation, and ANOVA with a significance level of 0.05. The mean age of students was 24.1±5.65. The total population of the study was 56% female and 44%, male. The results revealed that the prevalence of fatigue among students was moderate (56.60%). The status of harmful cell phone use was reported to be moderate (90%). There was a significant relationship between mobile phone use and total fatigue (p=0.029), decreased motivation (p=0.025), and mental fatigue (p = 0.001). Results showed that excessive use of cell phones had an adverse impact on total fatigue, mental fatigue, and motivation. Therefore, it is recommended to design effective interventions to prevent harmful use of cell-phone, student fatigue, and other consequences, including academic failure and reduction of mental health. [ABSTRACT FROM AUTHOR]