SummaryBackgroundSchool closures were part of a series of non-pharmacological intervention (NPI) measures addressing the COVID-19 pandemic in Cyprus. We aimed to study changes in the environment, diet, behavior, personal hygiene, contacts, lifestyle choices and the degree of compliance to NPI measures by primary school children in Cyprus at school and at home for two periods, i.e., before lockdown and during the school re-opening using the methodological context of the human exposome.MethodsDuring June 2020, an online survey questionnaire was forwarded to parents of primary school children through schools’ administrations, with questions about the children’s lifestyle/behaviours for two periods; school re-opening, following the population-wide lockdown (May 21-June 26, 2020), and the school period before lockdown (before March 2020). Descriptive statistics and exposome wide association analysis were implemented to agnostically assess associations of demographic, lifestyle and behavioral parameters with the degree of compliance to NPI measures.FindingsA total of 1509 children from more than 180 primary schools (out of 330 schools) in Cyprus were included. Median number of contacts per day at home, school and other places during weekdays was lower (pInterpretationIn this national survey, children showed a high degree of compliance to most NPI measures for the community and primary school settings in Cyprus. The initial NPI measures may have affected the children’s exposome profile in the following months, by altering their diet, physical activity, sedentary lifestyle and hand hygiene habits.FundingThe study was partially funded by the EXPOSOGAS project, H2020 under grant agreement #810995Panel: Research in contextEvidence before this studyWe searched PubMed for studies published until September 30, 2020 using the search terms: COVID-19, children and lifestyle. Only six peer-reviewed, English-language studies were retrieved on the effect of COVID-19 measures on children’s lifestyle. The impact of non-pharmacological intervention (NPI) measures on children’s health during the pandemic period has been sporadically studied by focusing on a few risk factors at a time without using the exposome’s methodological framework, which is defined as the comprehensive characterization of all environmental exposures during one’s lifetime.Added value of this studyA survey targeted all primary schools of Cyprus to comprehensively study the impact of the initial population-wide NPI measures (lockdown) (March 13-May 4) on the children’s exposome during the school re-opening period (May 21 – June 26). To the best of our knowledge, this is the first study looking at the post-confinement (lockdown) exposome profile changes of children during schools’ re-opening, after the initial population-wide NPI measures of COVID-19 response. The comprehensive and agnostic description of the children’s exposome profile may help to comprehensively account for both known and possibly unknown effects of NPI measures on children’s health and for delineating the children’s degree of compliance to infection prevention and control protocols at school and at home.Implications of all the available evidenceThis dataset could inform COVID-19 risk-based public health response strategies targeted for school settings. Future response strategies to epidemic waves shall consider elements of promoting a healthy lifestyle for children at school and at home. Public health policy could ultimately benefit from the inclusion of the human exposome methodological framework and its tools towards the improved identification of susceptible sub-population groups and to facilitate the deployment of site-tailored public health measures; this may be particularly relevant for children and their potential to spread the disease to vulnerable groups.