OBJECTIVE To determine the prevalence of and factors associated with depression and stress with perceived quality of life and the salivary cortisol levels in Community Health Agent (CHA). Materials and Methods Cross-sectional descriptive study of CHAs in Pelotas-RS, Brazil. Data collection, including sociodemographic information and factors related to work and health. Beck Depression Inventory (BDI) II was used to assess depressive symptoms, Inventory of Stress Symptoms Lipp (ISSL) was used for the analysis of stress and the WHOQOL-BREF was used to investigate quality of life. Salivary cortisol was quantified via ELISA test. RESULTS The assessments showed that 71.0% are in a state of stress resistance, 30.5% were in the alert state of stress and 32.8% were in the stress state of exhaustion. Depressive episodes (BDI≥12) were observed in 28.2%. The environmental domain had the lowest score for quality of life. We observed significantly higher salivary cortisol levels in CHAs with less than 1 year of service and with the lowest quality of life scores in the environmental subsection. CONCLUSIONS A high prevalence of stress and depression was observed in this sample of CHAs. In addition, the worst levels of quality of life were identified in the environmental subsection. Cortisol levels corroborate these findings regarding quality of life within the environmental domain and began working less than a year previously.