Background: Having multimorbidities may increase health problems. Moreover, health-related quality of life correlates negatively with the number of chronic conditions a patient has. Living alone has been identified as a predictor of poorer quality of life, and a sedentary lifestyle is widely known to increase health problems and mortality. Purpose: This study was designed to identify the effects of living alone and of sedentary behavior on health-related quality of life in patients with multimorbidities using nationally representative community data. Methods: A secondary data analysis of the Korea National Health and Nutrition Examination Survey was conducted. In this study, 1,725 adult patients aged 19 years and above with two or more chronic diseases were selected for the analysis. Health-related quality of life was measured using the European Quality of Life-5 Dimensions. Multiple logistic regression was performed to identify the effects of living alone and of sedentary behavior on health-related quality of life. The statistical analyses took into account the components of the complex sampling design such as the strata, clusters, weights, and adjustment procedures, and missing data were treated in a valid manner. Results: After adjusting for gender, age, employment status, and number of chronic diseases, it was found that the odds of having a high health-related quality of life were lower in single households than in multiperson households (odds ratio = 0.62, 95%confidence interval [0.46, 0.84]). In addition, after adjusting for gender, age, employment status, number of chronic diseases, and living arrangement, the odds of having a high health-related quality of life decreased as sedentary time increased (odds ratio = 0.93, 95% confidence interval [0.89, 0.96]). Conclusions/Implications for Practice: To improve quality of life in patients with multimorbidities, nursing interventions that support patients who live alone and have complicated disease-related issues and that reduce sedentary behavior should be developed.