Agegnehu Bante,1 Abera Mersha,1 Azene Tesfaye,2 Behailu Tsegaye,3 Shitaye Shibiru,1 Gistane Ayele,4 Meseret Girma4 1School of Nursing, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia; 2Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia; 3School of Medicine, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia; 4School of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, EthiopiaCorrespondence: Agegnehu BanteArba Minch University, PO Box 21, Arba Minch, EthiopiaTel +251-918-487-338Email agegnehubante@gmail.comIntroduction: COVID-19 is one of the huge general wellbeing crisis for the planet. Since its first recognition, over 90.2 and 1.9 million people are infected and dead, respectively. Although it is not easily available for low-income countries, after many trials vaccination is initiated by some industrialized nations. However, still now there is no effective treatment for the infection. Henceforth, adherence with COVID-19 preventive and control measures is the only option to stop its spread and minimize its disastrous impact, especially, in developing nations like Ethiopia. Knowledge and behavior change are pillars to engage with preventive measures. Thus, the motivation behind this study was to assess communities’ adherence with COVID-19 preventive measures and its associated factors among inhabitants of Dirashe district, Southern Ethiopia.Materials and Methods: A cross-sectional study was directed among 648 inhabitants in Dirashe district from June 20 to July 5, 2020. A multistage sampling technique was applied to select the participants. A pretested, validated and reliable interviewer-administered survey tool comprising the socio-demographic characteristics, knowledge (α = 0.78), and adherence with COVID-19 preventive measures (α = 0.73) was used. The data were assorted electronically using Open Data Kit (ODK) collect version 1.17.2 android application and exported to Stata version 15.0 for analysis. Adjusted odds ratio (aOR) with 95% CI was used to identify variables associated with the community’s adherence with COVID-19 preventive measures.Results: An aggregate of 644 inhabitants were participated in this study; of them, only 12.3% [95% confidence interval (CI): 9.8, 15.1] adhered to the recommended COVID-19 preventive measures. Likewise, 63.51% [95% CI: 59.7, 67.2] and 54.5% [95% CI: 50.6, 58.4] of the participants had good knowledge and favorable attitude towards COVID-19 preventive measures, respectively. Urban residence [aOR: 9.74, 95% CI: 4.72, 20.10], favorable attitude [aOR: 1.97, 95% CI: 1.05, 3.68] and concerned about COVID-19-related stigma [aOR: 2.43, 95% CI: 1.02, 5.79] were independently associated with communities adherence with COVID-19 preventive measures.Conclusion: In general, communities’ adherence to the recommended COVID-19 preventive measures was very low in the area. Addressing underprivileged population groups, disseminating teaching aids in local languages, behavioral change communications, and law enforcement is imperative to strengthen COVID-19 prevention practice.Keywords: coronavirus disease 2019, public adherence, knowledge, prevention practice, southern Ethiopia