Antecedents A substantial number of Mexican adults (9-13%) experience psychological distress and a significant minority suffers from severe mental impairment. Most people suffering from depression do not seek treatment, even though they can be helped and treated. In some families, depression may occur across generations, but it may also affect those without any family history. Low self-esteem, stressful life changes and chronic stress may provoke a depressive episode. In recent years, it has been demonstrated that medical conditions, such as cardio-vascular diseases, cancer, Parkinson’s disease and hormonal disorders, may lead to depression, making a sick individual apathetic, incapable of taking care of his/her physical needs. In turn, such apathy increases the recovery period. Most probably, a combination of genetic, psychological, and social factors work together in the development of a depressive disorder. However, very little is known about the principal causes of depression in Mexico. It is possible that, due to cultural and social differences, these factors and their impact are distributed differently on the Mexican population as compared to those from the US population. Objectives The first objective from this study is to estimate the frequency and distribution of depression by social characteristics on a population of health workers in Mexico. The second objective is to study the effect of stress and chronic diseases on depression. Methods To study the effects of stress and chronic diseases on depression we used a cross-sectional data obtained from a total of 4048 workers. These workers participated in the “IMSS Health Worker Cohort Study in Morelos” through the years 1998 to 2000. Their age varied from 18 to 89 years. A self-reported questionnaire was administered to obtain information on life-style factors, social characteristics, work stress, and chronic diseases. Data were analyzed using politomic regressions to study the effects of social characteristics on moderate and high levels of depressive symptomatology and on risk factors, such as work stress and chronic diseases. The analysis is stratified by gender as it is expected that effects of such characteristics vary by gender. Results Our results show that the workers’ socioeconomic characteristics are significantly associated with their depression level. Being female, being separated from the spouse, having lower education, and working in non-professional jobs with lower income is significantly and positively associated with depression. Similarly, having a less satisfying job and having more than one chronic disease is significantly and positively associated with depression. Workers from a lower socioeconomic status report higher levels of stress and suffer more chronic diseases compared to those from higher socioeconomic levels. Hence, some of the effects of social characteristics seem to be mediated by stress and chronic diseases. Conclusion Our results are consistent with previous research demonstrating systematic variations among groups of people who are at a higher risk for depression. In our study, we find that depression is higher among selected groups, such as women, young and old workers, those without a partner, and those with lower economic resources. We also find that stress and chronic diseases are among the reasons for which groups, which are socially and economically vulnerable, tend to become depressed. To be effective in the long run, any intervention directed to these groups of people must take into account associations highlighted in this paper.