Background: Long-term treatment with sodium valproate affects the lipid profile and serum HOMOCYSTEINE level. Studies have revealed different results in epileptic patients and there is very little data available regarding the effects of sodium valproate in serum HOMOCYSTEINE level and lipid profile in migraine patients. Objectives: The present study investigated the serum HOMOCYSTEINE level and lipid profile of migraine patients before and after sodium valproate prophylactic therapy. Methods: This study included 52 adult patients with migraines who were candidates for prophylactic migraine treatment by sodium valproate. None of the patients were affected by hyperlipidemia syndromes, cardiovascular disease, stroke, diabetes, gout, carotid stenosis, hypertension, and thyroid, metabolic, or hepatic disorders. The initial peripheral venous blood sample was collected before receiving sodium valproate. Patients received sodium valproate 500 mg daily. The second venous blood sample was taken 3 months later, during the treatment period. Serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and HOMOCYSTEINE were measured by standard methods. Results: Themeanserum levels of TC, HDL, TG, and HOMOCYSTEINE increased significantly three months after treatment with sodium valproate. The mean serum level of LDL increased after treatment, however, the difference was not significant. Conclusions: Sodium valproate increases the level of serum lipids in patients with migraines; therefore, the risk of cardiovascular diseases may increase by the long-term use of this drug as a prophylactic treatment in migraine patients. Consequently, in patients with other risk factors of cardiovascular disease, sodium valproate should be prescribed with caution.