Abstract Background Studies show that having some symptoms seems to be associated with more severe disease and poor prognosis. Therefore, knowing who is more susceptible to symptomatic COVID-19 disease is important to provide targeted preventive and management practice. The aim of the study was to assess factors associated with the development of symptomatic disease among COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia. Methods A case-control study was conducted from August to September 2020 among a randomly selected 730 COVID-19 patients (337 Asymptomatic and 393 Symptomatic patients). Chi-square test and independent t-test were used to detect the presence of a statistically significant difference in the characteristics of the cases (symptomatic) and controls (asymptomatic), where p-value of