The coronavirus disease 2019 (COVID-19) pandemic has devastated livelihoods and health systems globally. The pandemic resulted in the closure of businesses and schools and the remote provision of many services in order to mitigate the spread of the virus. In some instances, families stopped patronizing paid caregivers due to the fear of contracting the virus and financial concerns due to massive job losses. Even with the re-opening of schools, many families are reluctant to send their children back to school on an in-person basis. One key consequence of these disruptions is a significant increase in the need for childcare services, including assistance with schoolwork. Such a substantial increase in time requirements for childcare domestically has potential mental health consequences. We therefore ascertained the relationship between childcare and mental health in South Africa. Data came from the second and third waves of the National Income Dynamics Study-Coronavirus Rapid Mobile survey. The outcome was a depression index obtained from the two-item Patient Health Questionnaire while the main covariate was the average number of hours spent in taking care of children per weekday. Employing the ordered logit model, we found a positive relationship between spending more hours on childcare and worse mental health for caregivers, with the relationship generally stronger for men. We suspect that our results are lower bound estimates of the impact of time spent on childcare on mental health in South Africa. Furthermore, the childcare-mental health relationship was significantly mediated by childcare responsibilities preventing/mitigating the ability of caregivers to work as well as preventing caregivers from searching for jobs. These findings highlight the wider health implications of COVID-19 and the need to carefully consider potential policy responses aimed at containing the virus. We advocate a multi-stakeholder approach to mitigating the mental health impact of COVID-19 by encouraging conversations and input from government, school authorities, employers and parents/guardians.