After informed consent by parents and childcare workers, asymptomatic day care center–attending children and childcare workers participated in twice weekly self-sampling of respiratory secretions scheduled for a 12-week observation period (May to July 2021). Participants could initially choose between 3 study groups, including self-sampling of mouth-rinsing fluid (saliva sampling), followed by pooled polymerase chain reaction (PCR) testing and/or rapid antigen self-testing. (For children, this was performed by their parents.) Before and after the period of continuous testing, SARS-CoV-2 seroprevalence status of children and childcare workers was determined by finger-prick testing, and parents and childcare workers answered psychosocial questionnaires. In addition, qualitative interviews on participants’ attitudes in a subsample of parents and childcare workers were conducted.