Fibromyalgia patients who are exposed to extreme oxidative stress may face more severe clinical features or oxidative stress may be increased by the severity of the disease. The purpose of these investigation were to determine serum paraoxonase activities (PON-1) and nitric oxide (NO) activities and malondialdehyde (MDA) level in fibromyalgia and whether there were any associations between these enzymes activities, MDA level, and clinical parameters. The study groups were consisted of 30 primer fibromyalgia patients and 30 healthy subjects. Clinical findings, pain severity, functional disability, general health status, anxiety, and depression assessed, and serum PON-1 activity, MDA, and NO levels were measured. The primer fibromyalgia group had significantly higher MDA, low density lipoprotein-cholesterol (LDL-C), and decreased PON-1 activity, NO, and high density lipoprotein-cholesterol (HDL-C) with respect to controls. The paraoxonase activity was negatively correlated with MDA, LDL-C, Visual Analog Scale (VAS), Fibromyalgia Impact Questionnaire score (FIQ score), tender point score, age, and BDI score, while positively correlated with NO and HDL-C. MDA level was positively correlated with VAS, FIQ score, tender point score, age, and negatively correlated with NO level. These results suggest that FMS patients have an alteration in levels of MDA, NO, and PON-1 activities. We think that impaired oxidant/antioxidant status may affect the symptoms of the disease. Also, they may be of importance in the complex physiopathologic mechanism behind the development of FMS.