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Abstract Background Musculoskeletal disorders are common worldwide. Several factors are suggested in their aetiology, one of which is ergonomics alongside other individual factors. This study aims at investigating the prevalence of musculoskeletal disorders among administrative office workers at a large university in Saudi Arabia. Methods This cross-sectional study recruited office workers at a Saudi university. A questionnaire was used that involved three sections, the first section consisted of sociodemographic questions, the second included the Rapid Office Strain Assessment (ROSA) checklist to assess ergonomic factors possibly involved, and the third included the Nordic Musculoskeletal Questionnaire to measure the outcome. Bi-variate analyses were performed by Chi-Squared tests and T-tests where appropriate, and a multivariable logistic regression was done to yield odds ratios (OR) and 95% confidence intervals (CIs). Results The prevalence of musculoskeletal symptoms in any region during the past 12 months preceding the study was 84.5%, and only 30% have sought medical advice. The most common area of complaint was the lower back (54.5%). After adjustment, age and years of experience were positively associated with musculoskeletal symptoms (OR = 1.04, 95% CI = 1.01–1.09 and OR = 1.10, 95% CI = 1.05–1.15). Normal weight was associated with a significant reduction in risk (OR = 0.10, 95% CI = 0.05–0.18). ROSA score was an independent risk factor (OR = 1.77, 95% CI = 1.05–2.96). Conclusions Musculoskeletal symptoms were highly prevalent in the current sample. Identified predictors may support the need for interventions to reduce risk.