This study aimed to investigate sleep problems and comorbid conditions associated with fatigue in the general population.The data were obtained from a nationwide cross-sectional survey conducted in 2018. The Fatigue Severity Scale was used to assess fatigue. We examined sleep habits, such as workday sleep duration, chronotype, and free-day catch-up sleep, excessive daytime sleepiness (EDS), depression, and other comorbid conditions. We conducted multiple logistic regression analysis with the presence of fatigue as a dependent variable.Of 2,493 adults aged 19 to 92 years, 50% men, mean age was 47.9 ± 16.4 years. The average workday sleep duration was 7.1 ± 1.1 h, and the prevalence of fatigue was 31%. After adjusting for potential confounders, fatigue was associated with EDS (odds ratio [OR] 3.751, 95% confidence interval [CI] 2.928-4.805), depression (OR 3.736, 95% CI 2.701-5.169), perceived insufficient sleep (OR 1.516, 95% CI 1.249-1.839), free-day catch-up sleep (OR 1.123, 95% CI 1.020-1.235), less alcohol intake (OR 0.570, 95% CI 0.432-0.752), and physical inactivity (OR 0.737, 95% CI 0.573-0.948). On subgroup analysis, fatigue was additionally associated with short workday sleep duration (OR 0.899, 95% CI 0.810-0.997) in individuals without EDS. However, among those with EDS, only depression (OR 2.842, 95% CI 1.511-5.343) and less alcohol intake (OR 0.476, 95% CI 0.247-0.915) were associated with fatigue.Fatigue was significantly associated with depression independent of EDS. Further research is warranted to better understand the pathophysiological relationship between fatigue, depression, and sleep.