To identify potential protective mechanisms that might buffer the effects of the COVID-19 pandemic on well-being, the current set of studies (NStudy 1 = 1172, NStudy 2 = 451) examined the roles of hope and religious coping (positive and negative) in promoting well-being during periods when stringent stay-at-home orders were implemented in Colombia and South Africa to control the spread of SARS-CoV-2. After controlling for relevant sociodemographic characteristics (Studies 1 and 2), subjective health complaints, and sleep quality (Study 2), hope was positively associated with well-being and the relation between hope and well-being was moderated by religious coping. Whilst well-being was highest when levels of hope were high (irrespective of positive or negative religious coping levels), when reported hope was low, well-being tended to be higher when positive religious coping was high (Study 1) and negative religious coping was low (Study 2). Implications of the findings for maintaining well-being during a public health crisis are discussed.