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Background Monotonous and sedentary work is significantly associated with the worst health of workers. There is a scarcity of data investigating the musculoskeletal health of sedentary workers working in low-income and middle-income settings. This study aimed to measure the prevalence and predictors of musculoskeletal health complaints (MHC) among Bangladeshi shopkeepers. Methods This cross-sectional study was conducted in Dhaka, Bangladesh. Data from 1553 Bangladeshi shopkeepers aged 18 years and above were analyzed. MHC was measured using the musculoskeletal subscale of the subjective health complaints scale. The descriptive analysis helped to compute MHC prevalence and compare the prevalence across groups. Regression analysis revealed the predictors of MHC for the shopkeepers. Results The prevalence of MHC among shopkeepers was 58.0%. The prevalence of low back pain was the highest (55.5%), followed by neck pain (48.0%) and upper back pain (43.5%). Regression analysis identified sex (aOR 1.301, CI 0.996 to 1.700), age (aOR 1.405, CI 1.047 to 1.886), body mass index (aOR 0.495, CI 0.397 to 0.617), and substance abuse (aOR 1.998, CI 1.136 to 3.514) as independent predictors of MHC among the shopkeepers. Furthermore, significantly higher odds of MHC have been found among tobacco users (OR 1.234, CI 1.009 to 1.510). Conclusion This study revealed a high prevalence of MHC and unhealthy lifestyles among shopkeepers in Bangladesh. Shopkeepers should be provided with better health literacy to follow healthy lifestyles and prevent MHC among this cohort.