BACKGROUND: COVID-19 is a global pandemic caused by a transmissible respiratory virus, SARS-Cov-2. Because it is a novel pathogen, limited information is available to characterize the spectrum of clinical illness, transmission efficiency, and the duration of viral shedding for patients with COVID-19. Quarantine is an important component of a multilayered strategy to prevent sustained spread of COVID-19 everywhere. The aim of this study was to assess public perceptions toward quarantine for COVID-19 and associated factors among adult residents of selected towns in Southwest Ethiopia, 2020. METHODS: The community-based cross-sectional study was conducted from 1 to 15 June 2020 among adult residents of selected towns in south west Ethiopia. Systematic random sampling was used to select 844 participants. A structured and interviewer-administered questionnaire was used to collect data. Descriptive statistics were used to describe different variables. Multiple linear regression was carried out to determine the predictors of outcome variables. In multiple linear regression, variables with p-value <0.05 were taken as statistically significant association with community perception toward quarantine. RESULTS: The total of 816 study participants were interviewed from which 450 (55.1%) were male. The median age of respondents was 30 years. Four hundred and twenty-seven (52.3%) of the respondents have a positive perception toward quarantine. Factors associated with perception toward quarantine were having training on COVID-19 (ß=2.76, p=0.005), educational status of secondary (ß=2.73, p=0.001), educational status to above secondary (ß=2.24, p=0.011), occupational status of merchant (ß=1.73, p=0.020), and knowledge of COVID-19 (ß=0.23, p=0.001). CONCLUSION: Only 52.3% of the respondents have a positive perception toward quarantine. Having training on COVID-19, educational status of secondary and above, being a merchant, knowledge of COVID-19 and knowledge of quarantine were significantly associated with a positive perception toward quarantine. Concerned bodies should work on enhancing the awareness of the community through information education and communication/behavior changing communication materials.