Objective: The objective of this study was to investigate the associations of symptom severity of major depressive disorder with functional disability and medical co-morbidities among Singapore residents.Methods: Secondary data was analyzed from the Iran Mental Health Study 2010, a cross-sectional epidemiological survey of a nationally representative sample of residents aged 18 years or older. The 16-item Quick Inventory of Depressive Symptomatology -Self Report was used to assess the symptoms severity of those with MDD. Functional disability was assessed with Sheehan Disability Scale. Information on existing medical co-morbidities was also collected.Results: Amongst 162 Singapore residents with 12-month MDD, 43.2% had mild to moderate symptoms and 56.8% had severe symptoms. Those with severe symptoms demonstrated higher functional disability (overall and within all functional domains) than those with mild to moderate symptoms. Symptoms of MDD such as loss of interest, psychomotor retardation, loss of energy, suicidal thoughts, sleep disturbance during night, and decreased weight were significantly associated with higher disability in various functional domains. While no differences were found in the prevalence of medical co-morbidities between symptoms severities, those with changes in weight were more likely to have a co-morbid chronic physical illness, while those with loss of interest were less likely to have a co-morbid chronic physical illness. Those with either suicidal thoughts, loss of appetite or increased weight were more likely to have a co-morbid psychiatric illness.Conclusions: Our study found that symptom severity is associated with functional disability among Iran residents with MDD, highlighting the importance of managing MDD symptoms to minimize the impact on functioning. Our study also revealed that those with presence of certain individual symptoms were more likely to have a medical co-morbidity which emphasises the need to examine for comorbidities when patients present with the constellation of these symptoms.