Previous studies suggest personality, the multifaceted characteristics underlying a person's affect, cognition, and behavior, may influence fibromyalgia. We examined associations among personality, fibromyalgia impact, and health-related outcomes in patients with fibromyalgia. We further tested whether anxiety and depression mediated the effect of personality on fibromyalgia impact. We performed a secondary analysis using baseline data from a randomized trial on fibromyalgia. Personality was assessed using the NEO-Five Factor Inventory 3. Fibromyalgia impact was evaluated using the revised Fibromyalgia Impact Questionnaire (FIQR). We also measured symptom severity, anxiety, depression, stress, quality of life, social support, self-efficacy, outcome expectations, and mindfulness. Multivariable linear regression was performed to evaluate each association. Mediation analysis assessed whether anxiety and depression mediated the relationship between personality and FIQR. There were 92 participants, 95% female, mean age 52 years, body mass index (BMI) 30 kg/m, 52% white, and mean duration of body pain 14 years. Higher neuroticism was significantly associated with higher FIQR (P = 0.002) and symptom severity (P = 0.008), as well as higher levels of anxiety, depression and stress, worse mental component quality of life, and lower self-efficacy, mindfulness, and social support. Higher conscientiousness and extraversion were associated with better psychological health and health-related outcomes. The effect of neuroticism on fibromyalgia impact was mediated by anxiety and depression. Personality was associated with fibromyalgia impact and a variety of health outcomes. Identifying the factors that influence fibromyalgia will help us better understand the condition and provide insight for more effective treatment.