A register-based retrospective observational study was conducted to describe SARS-CoV-2 cases and case-clusters in schoolchildren of Danish primary and lower secondary schools and identify which factors were associated with the occurrence of case-clusters in schools. The study period was the autumn school semester 2021. Clusters were defined as three or more cases in a school-class level within 14 days. Descriptive analysis was carried out and multivariable logistic regression analysis was performed to determine which factors were associated with case introductions (i.e., primary case) being linked to a cluster. More cases and clusters were identified in lower than in higher class levels. Out of 21,497 cases introduced into a school, 41.6% started a cluster. A higher assumed immunity level in a class level was significantly reducing the odds of a case introduction being linked to a cluster (e.g., assumed immunity of ≥80% vs <20%: OR: 0.28; 95%CI: 0.17-0.44). A previous infection (in the primary case) had a protective effect (OR: 0.58; 95%CI: 0.33-0.99). This study suggests that most cases appearing in schools did not induce clusters, but that once cluster occur sizes can be large. It further indicates that vaccination of children markedly reduces the risk of secondary infections.