Depression and chronic medical disorders are strongly linked. There are limited studies addressing the correlates of the severity of depression in patients with co-morbid disorders in primary care settings. This study aimed to identify the socio-demographic and disease-specific risk factors associated with the severity of depression at baseline among patients participating in a randomized controlled trial (HOPE study). Participants were part of a randomized controlled trial in 49 primary care health centers in rural India. We included adults (≥ 30 years) with at least mild Depression or Anxiety Disorder and at least one Cardiovascular disorder or Type 2 Diabetes mellitus. They were assessed for the severity of depression using the PHQ-9, severity of anxiety, social support, number of co-morbid chronic medical illnesses, anthropometric measurements, HbA1c, and lipid profile. Proportionately there were more women in the moderate category of depression than men. Ordinal logistic regression showed co-morbid anxiety and a lower level of education significantly increased the odds of more severe depression, while more social support was significantly negatively associated with depression severity in women. In men, anxiety was positively associated with greater depression severity; while reporting more social support was negatively associated with depression. This is a cross-sectional study and thus, no causal conclusions are possible. Anxiety and poor social support in both genders and lower educational levels in women were associated with increased severity of depression. Early identification of risk factors and appropriate treatment at a primary care setting may help in reducing the morbidity and mortality associated with depression.