<p>Fibromyalgia involves symptoms of pain, sleep disruption, and fatigue, which can have a deleterious impact on mental and physical health, and role functioning. Health self-efficacy, the perceived ability to manage and cope with health problems, may mitigate risk for functional disability and improve health perceptions. As a contributor to goal-oriented motivation, self-efficacy may facilitate hope and reduce hopelessness, thereby promoting willingness and motivation to engage in functional activities, with consequent benefit to perceived health. Our sample of 416 persons with self-reported fibromyalgia completed assessments of health self-efficacy, hope, hopelessness, role functioning, and general health. We conducted serial mediation linear regression analyses, covarying age, sex, and race/ethnicity. Supporting hypotheses, greater health self-efficacy was related to more hope and less hopelessness and, in turn, to fewer role limitations due to physical/emotional difficulties and, consequently, to better health perceptions (<i>p</i> &lt; .001). Self-efficacy may facilitate health promotion engagement and use of adaptive coping (e.g., goal-setting; problem-solving), resulting in greater hope and less hopelessness, with downstream benefits for role functioning and health perceptions, perhaps as a result of strengthened motivation and determination to manage health, reduced negative emotionality, and enhanced perceptions of role capabilities. Healthcare providers should consider promoting self-efficacy and hope, and reducing hopelessness, perhaps via Cognitive Behavioral Therapy or self-management strategies, and by fostering interpersonal wellbeing, to facilitate role functionality and improve health perceptions in individuals with symptoms of fibromyalgia.</p>