Objectives: The COVID-19 pandemic has caused unseen pressure on healthcare systems in many countries, jeopardizing the mental well-being of healthcare workers. The authors aimed to assess the mental well-being of Finnish healthcare workers from 2 hospital districts (Helsinki University Hospital [HUS] and Social and Health Services in Kymenlaakso [Kymsote]) with differing COVID-19 incidence rates during the first wave of the COVID-19 pandemic in spring 2020. Material and Methods: A total number of 996 healthcare workers (HUS N = 862, Kymsote N = 134) participated in this prospectively conducted survey study during summer 2020. Symptom criteria of self-reported mental health symptoms followed ICD-10 classification, excluding duration criteria. Participants were divided into symptom categories “often/sometimes”, and “rarely/never”. These groups were compared to sociodemographic factors and factors related to work, workload, and well-being. Results: The degree of mental health symptoms did not differ between the 2 healthcare districts despite differing COVID-19 incidences (p = 1). The authors observed a significant relationship between self-reported diagnostic mental health symptoms and experiences of insufficient instructions for protection against COVID-19 (in HUS cohort p < 0.001), insufficient recovery from work (p < 0.001), and subjective increased workload (p < 0.001). Conclusions: The authors’ results show the importance of well-planned and sufficient instructions for protection from SARS-CoV-2 for healthcare workers, indicating their need to feel safe and protected at work. The workload of healthcare workers should be carefully monitored to keep it moderate and ensure sufficient recovery. Sufficient control of the epidemic to keep the burden of the healthcare system low is vital for healthcare workers’ well-being. Int J Occup Med Environ Health. 2022;35(6):708–18