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Aim and Background: One of the serious problems in organizations is absenteeism from work that seems to be affected by personnel&rsquo;s psychological status and personality characteristics. The aim of this study was to determine the relationship of psychological and personality factors with absenteeism from &lrm;work among university staff. Methods and Materials: The present study was a cross-sectional survey. From among a total of 21504 employees of Isfahan University of Medical Sciences (Iran), 250 individuals were selected using quota sampling. With the approval of the management of the human resources and development and other sectors, a demographic characteristics questionnaire, the Depression, Anxiety, Stress Scale (DASS), and the NEO Five-Factor Inventory (NEO-FFI) were completed. Data were analyzed in SPSS software using Pearson correlation and point biserial correlation coefficient. Findings: Absenteeism had a positive significant relationship with stress level, neuroticism, age, work experience, number of children, and employment type (P < 0.05). The lowest rate of absenteeism was observed among employees with doctoral education or with primary education and illiterate employees. The highest rate of absence was seen among formal employees. The mean depression and anxiety scores of the university staff were slightly lower than the general population, but their stress symptoms were slightly higher than those of the general population. Conclusions: The finding indicated that absenteeism from work is related to psychological traits and psychopathological symptoms. Absenteeism may be a dysfunctional avoidance response to psychological, social, and mental health status. According to these findings, stress coping skills training in the form of in-service training seems necessary. Moreover, employment analysis and assigning of positions based on psychological status and skills is suggested.