Background: Fatigue has been reported in 53-100% of patients with heart failure (HF). Fatigue in HF is described as a highly burdensome symptom that has a profoundly negative effect on quality of life and is associated with worsening prognosis and mortality. Despite its prevalence and deleterious outcomes, HF-related fatigue remains poorly understood with limited treatment modalities. Purpose: The purpose of this dissertation was to (1) describe known physiologic, psychologic, and situational correlates of HF-related fatigue, (2) evaluate the contribution of select physiologic variables to HF-related fatigue, and (3) identify correlates of excessive daytime sleepiness (EDS) in chronic stroke survivors as groundwork for future studies examining fatigue in HF. Methods: The first manuscript is a synthesis of the scientific literature on known correlates or mechanisms of HF-related fatigue. The second manuscript uses cross-sectional data from the 2015-2018 National Health and Nutrition Survey (NHANES). A complex sample design was used to assess the contribution of select physiologic variables on HF-related fatigue. Independent t tests and chi-square tests were used to explore differences between fatigued and non-fatigued adults and logistic regression to calculate the odds of having fatigue. Non-parametric correlations and descriptive statistics were used in the third manuscript to describe the relationship of EDS to sleep quality, body mass index (BMI), systemic inflammation, and energy metabolism of platelets in chronic stroke survivors. Results: Correlates of HF-related fatigue include age, sex, dyspnea, pain, disease severity, use of diuretics, volume status, anemia, oxygen uptake, depression, anxiety, perception of symptoms/health, sleep disturbances, poor social support, reduced quality of life. Concepts were grouped into 5 categories: individual, physiologic, psychologic, situational and outcome. Analysis of NHANES data revealed a low serum osmolality was significantly associated with fatigue (χ2 = -2.37, p = .03). Being female was predictive of experiencing fatigue when controlling for age, serum osmolality, serum hemoglobin and the presence of dyspnea (OR 4.68, 95% CI .34 – 2.75). The analysis of the pilot data found EDS in 27.3% of the sample. No statistical correlations were found between EDS, inflammatory markers, energy metabolism of platelets, sleep quality or BMI. A non-significant moderate effect size was noted with IL1-β (rho.42) and TNF-α (rho .35) and EDS. A small effect size was noted with IL-6 and EDS (rho .26). Conclusions: Improving our knowledge of mechanisms of HF-related fatigue will inform strategies to reduce or ameliorate the symptom. Future studies should continue to assess the relationship between serum osmolality, sex hormones and cellular energy metabolism to fatigue in patients with HF.