The determinants influencing individuals’ decisions to take part in serosurveys remain insufficiently explained. Examining perceptions from several viewpoints—including those of both participants and data collectors—within a comprehensive framework such as the socio-ecological model allows for consideration of influences operating at the individual, interpersonal, and structural levels of research participation. We applied a mixed-methods design to describe motivations and deterrents related to serosurvey participation in communities in Zambia’s Southern Province, where a serosurvey took place in 2016.During the initial phase, focus group discussions and in-depth interviews were carried out with 24 data collectors involved in a measles–rubella serosurvey in 2016. In the subsequent phase, 34 caregivers attending health facilities were surveyed to identify perceived facilitators and barriers to participation. Themes that emerged were organized according to the socio-ecological model, encompassing individual, interpersonal, and structural domains. Similar patterns were identified across responses from data collectors and caregivers. At the individual level, incentives encouraged participation, whereas certain religious beliefs were noted as obstacles to involvement in serosurveys. At the interpersonal level, household relationships and peer influences within the community could either promote or discourage participation. Community health workers were repeatedly highlighted as key enablers. At the structural level, concerns were raised regarding the process of specimen collection, the criteria for participant selection, and the failure to receive test results. The most commonly cited facilitator was receiving clear information about the purpose of the serosurvey (85% of respondents). The most frequently reported barrier was uncertainty about how collected blood samples would be used (53% of respondents). Regarding collection methods, caregivers consistently favored finger-prick blood sampling compared with venous blood draws or oral swabs. Overall, participation in serosurveys was considered acceptable by most respondents. Application of the socio-ecological model identified specific barriers and facilitators that can inform strategies to enhance participation, including in ongoing SARS-CoV-2 serosurveys. Future serosurveys should strengthen community engagement by explaining blood collection procedures in advance and clearly communicating study objectives through trusted intermediaries such as community health workers and traditional leaders.
