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The study aimed at investigating the causes and effects of stress encountered by library staff of the University of Ghana, Kwame Nkrumah University of Science and Technology and the University of Cape Coast and the various categories of stress. Using the purposive, simple random and convenience sampling techniques, the researcher sampled 153 respondents from UG, KNUST and UCC to respond to the questionnaire and interview questions. Descriptive statistics (Means and Standard Deviation), inferential statistics (Multiple Regression and ANOVA) were used for the quantitative analysis while content thematic analysis was used for the qualitative analysis. The study among other things found that poor administrative support, lack of support systems, lack of in-service training and inadequate resources, anxiety and frustration, staff conflict, ill-health and smoking and drinking were the major causes of stress among public university library staff in Ghana. However, it was revealed that library staff also adopt numerous coping strategies such as taking time off work and leave, positive thinking, building a strong human relationship and going for counselling in an attempt to manage their stress. It was recommended that universities institute proactive guidance and counselling measures, strong social support systems and compensation for additional work.