The exponential growth of e-commerce has intensified demand for rapid and reliable logistics, positioning warehouse loading and unloading as critical yet highly labor-intensive functions. These operations expose workers to significant occupational health risks, particularly musculoskeletal disorders (MSDs), due to repetitive lifting, awkward postures, and time pressure. This study investigates the prevalence and severity of musculoskeletal discomfort among warehouse workers engaged in loading and unloading tasks in Indian e-commerce facilities. Using the Cornell Musculoskeletal Discomfort Questionnaire (CMDQ) and Rapid Entire Body Assessment (REBA), data were collected from 450 workers across fulfilment centres and cross-dock sites. Findings reveal that 58.4% of workers reported musculoskeletal complaints, with the lower back, shoulders, and knees being most affected. REBA scores indicated predominantly medium to high ergonomic risks, especially during truck–dock transfers and overhead placements. The results underscore a strong association between postural risk and MSD prevalence, exacerbated during peak-season surges with untrained temporary labor. The study highlights the need for ergonomic interventions, including lift-assist technologies, standardized pallet heights, dock redesign, and purposeful task rotation. Beyond operational efficiency, integrating worker well-being into e-commerce logistics design is essential for sustainable supply chain performance.