Mounting evidence suggests fibromyalgia (FM) symptoms are influenced by dysfunction of the hypothalamic-pituitary-hormonal axes (HPHA) and the immune response system. The predominant FM symptoms of widespread pain, fatigue, sleep disturbance, depression, stiffness and exercise intolerance are related to abnormal levels of growth hormone (GH) and are reminiscent of "sickness behavior"; a syndrome initiated by the production of pro-inflammatory cytokines in response to various stressors. Cognizant of the reciprocal relationship between HPHA activity and the immune response system, we hypothesized that serum cytokine levels and FM symptom severity would be higher in FM patients with defective growth hormone response to exhaustive exercise compared to those without. Outpatients with FM (n = 165) underwent a Modified Balke Treadmill Protocol and GH response to exhaustive exercise was measured in peripheral blood samples. Levels of IL-1α, IL-1β, IL-1RA, IL-6, IL-8, IL-10, and TNF-α were measured from stored serum on a subset of 24 participants (12 with and 12 without normal GH response to exhaustive exercise). FM symptom severity was assessed using the Fibromyalgia Impact Questionnaire (FIQ), number of tender points and cumulative myalgic scores. GH dysfunction was associated with increased pain scores on the FIQ (p = 0.024), a greater number of tender points (p = 0.014), higher myalgic scores (p = 0.001) and higher pre-exercise levels of inflammatory cytokines IL-1α (p = 0.021), IL-6 (p = 0.012), and IL-8 (p = 0.004). These results suggest that a defective growth hormone response to exercise may be associated with increased levels of blood cytokines and pain severity in FM patients.