Mood disorders are more prevalent in individuals with chronic physical illness compared to individuals with no such illness. These disorders amplify the disability associated with the physical condition and adversely affect its course, thus contributing to occupational impairment, disruption in interpersonal and family relationships, poor health and suicide. This study used data collected in the Canadian Community Health Survey, cycle 3.1 (2005) to examine factors associated with comorbid mood disorders and to assess their association with the quality of life of individuals living in Ontario. Results indicate that individuals with chronic fatigue syndrome, fibromyalgia, bowel disorder or stomach or intestinal ulcers had the highest rates of mood disorders. The odds of having a comorbid mood disorder were higher among women, the single, those living in poverty, the Canadian born and those between 30 and 69 years of age. The presence of comorbid mood disorders was significantly associated with short-term disability, requiring help with instrumental daily activities and suicidal ideation. Health care providers are urged to proactively screen chronically ill patients for mood disorders, particularly among the subgroups found to have elevated risk for these disorders.