BackgroundAs a result of the coronavirus disease 2019 (COVID-19) outbreak, many countries have imposed movement restrictions and implemented lockdowns. However, evidence from a variety of nations showed that the COVID-19 outbreak and its associated quarantine measures triggered a wide range of psychological problems, such as anxiety, depression, and stress in the general population. As a result, the purpose of this study was to determine the prevalence and predictors of depression, anxiety, and stress symptoms among Tepi town residents during the pandemic lockdown.MethodologyA community-based cross-sectional survey was conducted among residents of Tepi town from September 15 through September 25, 2020, and residents who have lived in Tepi town for at least 6 months were included. We have employed the depression, anxiety, and stress scale 21 (DASS-21) to evaluate depression, anxiety, and stress. The Chi-squared test of association and logistic regression were used to identify factors associated with depression, anxiety, and stress among residents of Tepi town. For all statistical analysis, we used (IBM) SPSS version 25.ResultsAccording to the current study, the prevalence of depression, anxiety, and stress symptoms were 37.7%, 39.0%, and 44.2%, respectively, among residents of Tepi town. Estimated odds of having depression, anxiety, and stress were as follows: for being female 6.315, 4.591, and 3.155; smoking 1.787, 1.883, and 1.787; sleep problem 2.613, 2.254, and 1.721; chewing Khat 2.156, 2.053, and 2.110; quarantine for 14 days 2.251, 1.902, and 1.960; and frequent use of social media 3.126, 1.849, and 3.126 times more likely as compared to their corresponding reference group respectively. The odds of developing depression and anxiety respectively were as follows: for alcohol consumption 2.438 and 1.797 times higher than their corresponding reference group respectively. Those exposed to COVID-19 were 3.870 times more likely to develop depression symptoms. Estimated odds of having anxiety and stress symptoms for fear of COVID-19 were 1.776 and 1.835; social interactions altered were 3.197 and 2.069, moderate levels of hope were 2.687 and 2.849 respectively. The odds ratio for those taking traditional preventive medicine, and having family members infected with COVID-19 were 2.475 and 1.837 times more likely to experience anxiety symptoms respectively.ConclusionIn this study, the prevalence of depression, anxiety, and stress symptoms was found to be high among residences in Tepi town. Being female, chewing Khat, smoking, being quarantined for 14 days, frequently using social media, and having sleeping problems were all found to be significantly associated with an increased risk of developing depression, anxiety, and stress symptoms, whereas alcohol consumption and family members infected by COVID-19 were considerably linked to depression and anxiety symptoms. Fear of COVID-19, influence on social interaction and having a moderate level of hope were substantially related to stress and anxiety symptoms, while taking preventive medicine was found to be a significant factor in anxiety symptoms among Tepi town residences. Interventions should be made to improve the mental health of Tepi residents.