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Abstract Background Work urgency, accuracy and demands compel the computer professionals to spend longer hours before computers without giving importance to their health, especially body weight. Increase of body weight leads to improper Body Mass Index (BMI) may aggravate work related musculoskeletal discomfort and occupational-psychosocial stress. The objective of the study was to find out the effect of BMI on work related musculoskeletal discomforts and occupational stress of computer workers in a developed ergonomic setup. Methods A descriptive inferential study has been taken to analyze the effect of BMI on work related musculoskeletal discomfort and occupational-psychosocial stress. A total of 100 computer workers, aged 25-35 years randomly selected on convenience from software and BPO companies in Bangalore city, India for the participation in this study. BMI was calculated by taking the ratio of the subject's height (in meter) and weight (in kilogram). Work related musculoskeletal discomfort and occupational stress of the subjects was assessed by Cornell University's musculoskeletal discomfort questionnaire (CMDQ) and occupational stress index (OSI) respectively as well as a relationship was checked with their BMI. Results A significant association (p < 0.001) was seen among high BMI subjects with their increase scores of musculoskeletal discomfort and occupational stress. Conclusion From this study, it has been concluded that, there is a significant effect of BMI in increasing of work related musculoskeletal discomfort and occupational-psychosocial stress among computer workers in a developed ergonomic setup.