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Purpose: To evaluate the association of sleep duration with health-related quality of life (HRQOL) and examine the influence of age, sex, and common comorbidities on this association., Methods: Using appropriate survey design, we analyzed 50,181 adults who participated in the 2007-2015 Korea National Health and Nutrition Examination Survey. Participants were categorized into five groups according to self-reported sleep duration ≤ 5 (short sleeper), 6, 7, 8, and ≥ 9 h (long sleeper). HRQOL was measured with the European Quality of Life-5 Dimensions (EQ-5D) index and visual analogue scale (VAS)., Results: In multiple linear regression, short sleep duration was associated with lower EQ-5D index (β = - 0.024; 95% confidence interval [CI], - 0.027 to - 0.021) and lower EQ-VAS (β = - 3.0; 95% CI, - 3.7 to - 2.3), and long sleep duration was associated with lower EQ-5D index (β = - 0.016; 95% CI, - 0.021 to - 0.011) and lower EQ-VAS (β = - 2.2; 95% CI, - 3.1 to - 1.3) compared with 7-h sleepers. Old-age (≥ 65 years old) short and long sleepers had significantly lower EQ-5D index than those of < 65 years old. When separated according to sex, men with long sleep and women with short sleep showed the lowest EQ-5D index. Short and long sleepers with hypertension, diabetes, hypercholesterolemia, cardiovascular disease, or depression showed significantly lower EQ-5D index than those without comorbidities., Conclusions: Extreme sleep duration was associated with poor HRQOL. Short and long sleepers with old age and comorbidities had significantly lower HRQOL than those without such conditions.