BackgroundScabies is a neglected tropical disease affecting more than 200 million people worldwide every year. Scabies in school adolescents and young adults could affect their school performance. The current study investigates the factors associated with an outbreak of scabies at primary schools in southern Ethiopia.MethodA team of health professionals investigated an outbreak of scabies that occurred in primary schools from May 1 to 30, 2018. An unmatched case–control study was employed to assess factors which predisposed for the scabies outbreak. Cases of scabies were individuals having a skin lesion compatible with the WHO case definitions of scabies. Controls were from the same locality with no skin lesions. Data on sociodemographic and behavioral variables were collected using questionnaires. Data on clinical presentations of scabies among cases were recorded by two trained and experienced health professionals. Factors associated with scabies were assessed using bivariate and multivariate logistic regression, and strength of association was described using odds ratio (OR) and 95% confidence intervals (CIs).ResultsA total of 711 (237 cases and 474 controls) study subjects participated in the study. The mean age of study participants was 17.56±2.66 years. Poor knowledge about scabies, adjusted odds ratio (AOR)=4.32 (95% CI: 2.93, 6.36); male sex, AOR=2.69 (95% CI: 1.82, 3.96); and parental illiteracy, AOR =3.49 (95% CI: 2.06, 5.94) predicted scabies infestation. Additionally, socioeconomic variables like sharing clothes/beds or contact with others, AOR=3.12 (95% CI: 2.12, 4.59); low household annual income, AOR=2.13 (95% CI: 1.32, 3.44); and family size greater than five, AOR=1.77 (95% CI: 1.04, 3.01) were significantly associated with scabies infestation. Inaccessibility and poor utilization of water, AOR=1.64 (95% CI: 1.12, 2.40) and poor personal hygiene, AOR=1.69 (95% CI: 1.14, 2.51) were also factors independently associated with scabies.ConclusionModifiable risk factors such as personal hygiene and literacy level were found to be independent predictors of scabies infestation. Access to and utilization of water were also important predictors. Strategies for poverty alleviation and awareness creation on personal hygiene and efficient use of water are recommended for effective prevention of scabies infestation in closed institutions.