Work stress on civil servants in Indonesia is increasing in line with modernization and demands for public services. High work stress results poor physical and mental health, low job satisfaction, increased fatigue, and work accidents. This study aims to explain the influence of work stressors on work stress response by considering the role of individual characteristics and coping strategies as mediators. A cross-sectional study with an explanatory research approach was conducted randomly on 130 civil servants at the State Treasury Office in South Sulawesi. The Brief Job Stress Questionnaire (BJSQ) was used to assess work stressors and work stress responses, and The Brief COPE was used to assess coping strategies. Path analysis evaluates the relationship between individual characteristics, coping strategies, stressors, and work stress responses. The results showed that high work stressors were associated with decreased coping strategies (p-value <0.05) but low work stressors were positively associated with decreased stress responses (p-value <0.001). Individual characteristics were associated with an increase work stress response (p-value <0.001) but could not increase the effect of work stressors on the stress response. Likewise, coping strategies cannot reduce the effect of work stressors on stress response (Estimated value <0.525). Individual characteristics and coping strategies do not affect the relationship between stressors and work stress responses. Work stress management in controlling work stressors still needs to be done to minimize the risk of work stress in civil servants.