BACKGROUND: The coronavirus 2019 (COVID-19) pandemic had several mental effects on medical staff. OBJECTIVE: This study intended to evaluate deviations in Frontline Dental Staff (FDS) depression, perceived stress and hypochondria during the COVID-19 outbreak, and to assess whether the existence of potential risk-factors influenced these symptoms over time. METHODS: This prospective cohort study surveyed FDS three periods from February 1, 2021 to April 8, 2022. FDSs’ mental health was assessed through Beck Depression Inventory, Cohen Perceived Stress and the Evans Self-Illness Questionnaires; multivariate linear regression were used to identify potential factors associated with changes on each outcome (depression, perceived stress and hypochondria) over time. All analyses were performed in STATA ver.14. RESULTS: In a total of 635 FDS, about 69%, 83%, and 71% reported relative depression, 77%, 87%, and 64% reported moderate to high stress level, and 60%, 76% and 74% reported moderate hypochondriac from first, second, and third survives, respectively. The mean and standard deviation of the variables increased dramatically at second survive (July 17 to October 21, 2021) and decreased again at third survive significantly. Being female, working in public sector, and low socioeconomic level were main predictors of higher levels of depression (p < 0.001) and perceived stress (p < 0.001). Perceived stress was a strong predictor of high-level depression (t  =  7.79, p < 0.001). CONCLUSION: FDSs’ depression, stress and hypochondria were high and positively associated with being female, working in public-sector, and low socioeconomic level. To increase the effectiveness and decrease work burnout, psychological support should be provided.