Purpose: To determine factors affecting the presence of self-reported fatigue in middle-aged and older individuals. Some of the factors investigated include age, sex, cortisol levels, health status, education level, stress, cortisol levels, minutes of sleep, psychological stress, and joint pain. Methods: Data from the Midlife Development of the United States 2 (MIDUS 2) as well as the Stress Study was used for this thesis. The sample consisted of adults living in the coterminous of the United States ages 30-85. Data was previously collected through phone interviews as well as a questionnaire. Results: The prevalence of fatigue in the sample is approximately 58%, and higher in women than men independent on the age group. The predictors of the presence of fatigue were different between healthy men and women and individuals with disease. Predictors of fatigue included presence of joint pain, highest education level completed, self-reported stress, age, and the negative affect of stress which measured psychological stress. Conclusion: The determinants of fatigue are different between men and women as well as individuals that have the presence of disease.