ObjectivesTo identify sociodemographic and illness-related factors associated with quality of life among people with Schizophrenia.MethodsA hospital-based cross-sectional study design was employed among 351 people with schizophrenia and attending the followup service at Jimma University Medical Center, psychiatric clinic during the study period. Participants were recruited using a systematic random sampling method and a sample fraction of two was used after the first person was identified by a lottery method. Data entry was done using EpiData version 3.1 and then exported to Statistical Package for Social Sciences version 25 for analysis. Multiple regression analysis was used to determine the statistically significant association between quality of life and independent variables.ResultsAmong the four domains of quality of life, respondents scored the lowest mean in the social relationships domain (10.14 ± 3.12). Final adjusted multiple regression model revealed, being divorced was negatively associated with the physical domain (β = −0.72, p = 0.02), having no formal education was negatively associated with physical health domain (β = −0.69, p = 0.001) and age was positively associated with the psychological domain (β = 0.371, p = 0.071). Being rural resident was negatively associated with physical domain (β = −0.48, p = 0.01), with environmental domain (β = −0.64, p = 0.03), with social relationships domain (β = −0.45, p = 0.04), and with overall quality of life (β = −1.93, p = 0.006). Positive symptoms (β = −0.22, p = 0.001), negative symptoms (β = −0.36, p = 0.001), and general psychopathology (β = −0.098, p = 0.006) were inversely associated with overall quality of life.ConclusionIn this study, the social relationship domain of quality of life among people with schizophrenia has the lowest mean score. Some socio-demographic variables and psychiatric symptoms were found to be key significant associated factors of quality of life. Priority interventions to improve the social deficits and addressing psychiatric symptoms of people with schizophrenia is essential to improve their quality of life.