The COVID-19 pandemic has wrought acute harm to global mental health, especially among vulnerable populations. We explore what factors in people’s lives buffered the impact of the pandemic on depression; in particular, the role of social resources, economic resources, religiosity, and quality of their local environment. Drawing on three waves of longitudinal cohort data (two pre-pandemic waves and one pandemic-period wave) from primary caregivers of school-aged children in Ireland, we demonstrate that symptoms of depression increased sharply during the pandemic. However, depression symptomology increased less steeply among caregivers who, pre-pandemic, had greater economic resources and lived in higher quality environments, but especially among those with greater social resources and those who exhibited greater religiosity. Path analysis suggests that different sources of buffering might mitigate harm via different pathways. While most buffering factors appear to cushion mental well-being by reducing stresses from increased care work, improving familial relations, and helping caregivers manage the closure of/return to schools, other drivers appear to cushion mental well-being by reducing health anxieties around COVID-19, increasing opportunities for outdoor exercise, and protecting household incomes. This study highlights how crisis-preparedness should invest in social infrastructure alongside medical infrastructure to protect societies from future pandemics.