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The impacts of pandemics are recognized to go beyond infection, physical suffering, and socio-economic disruptions. Other consequences include psychological responses. Using a mental wellbeing lens, we analyzed COVID-19-related stressors in healthcare workers (HCWs) and community members who provided and regularly accessed health services in South Africa, respectively. From February to September 2021, during the second COVID-19 wave we conducted a qualitative study in one urban and one rural district. In-depth interviews and focus group discussions were used to collect data among 43 HCWs and 51 community members purposely and conveniently selected. Most participants experienced mental health challenges regarding multiple aspects of the COVID-19 pandemic and its resulting lockdown, with a few reporting positive adjustments to change. COVID-19 impacts on mental health were consistent among both HCWs and community members in urban and rural alike. Participants’ COVID-19-induced psychological responses included anxiety and fear of the unknown, perceived risk of infection, fear of hospitalization, and fear of dying. Physical effects of the pandemic on participants included COVID-19 infection and associated symptoms, possibilities of severe illness and discomfort of using personal protective equipment. These distresses were exacerbated by social repercussions related to concerns for family wellbeing and infection stigma. Lockdown regulations also intensified anxieties about financial insecurities and social isolation. At times when common coping mechanisms such as family support were inaccessible, cultural consequences related to lack of spiritual gatherings and limited funeral rites posed additional stress on participants. In preparation for future public health emergencies, recognition needs to be given to mental health support and treatment.