Background: Depression is common in many chronic physical health disorders, but the nature and extent of physical health comorbidities in depression, particularly within large population-based samples of patients, and how these comorbidities relate to factors such as age, sex, and social deprivation, are unknown. We aimed to assess the nature and extent of multiple physical health comorbidities in primary care patients with depression within a large and representative Scottish dataset. Method: This study was a cross-sectional secondary data analysis of 314 primary care practices in Scotland (from the Primary Care Clinical Informatics Unit at the University of Aberdeen, Scotland, March 31, 2007), including 143,943 people with depression and 1,280,435 controls. The outcomes assessed were 32 common chronic physical health conditions, adjusted for age, sex, and social deprivation. Depression was defined as a Read code for depression recorded within last year and/or 4 or more antidepressant prescriptions (excluding low-dose tricyclic antidepressants) within the last year. Results: Individuals in primary care with depression were more likely than individuals without depression to have every one of the 32 comorbid physical conditions we assessed, even after adjusting for age, sex, and deprivation. The depression group was also significantly more likely to have multiple levels of comorbidity, including 2 physical health conditions (OR = 1.55; 95% CI, 1.53-1.58), 3 physical health conditions (OR = 1.84; 95% CI, 1.81-1.87), 4 physical health conditions (OR = 2.06; 95% CI, 2.01-2.11; P < .001), and 5 or more physical health conditions (OR = 2.65; 95% CI, 2.59-2.71; P < .001). Conclusion: Depression in primary care is associated with a very wide range of physical health comorbidities and considerable medical burden. The nature and extent of this multimorbidity and the important association with social deprivation have not been previously described within a large and representative dataset of routine primary care data. Our findings have important implications for the integrated management of depression and physical health problems in the United Kingdom and throughout the world.