The purpose of this study is determine if the combination of zonisamide SR and bupropion SR are is more effective than either drug given alone or placebo in the treatment of obesity.

Inclusion Criteria:

• Female or male subjects, 18 to 65 years of age
• Have body mass index (BMI) ≥ 30 kg/m2 and ≤ 45 kg/m2 for subjects with uncomplicated obesity, and BMI of ≥ 27 kg/m2 and ≤ 45 kg/m2 for subjects with obesity and dyslipidemia and/or controlled hypertension
• Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to screening
• Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of adrenergic blockers and clonidine. Medical regimen must be stable for at least 6 weeks prior to randomization
• Triglycerides <400 mg/dL. Medications for treatment of dyslipidemia are allowed with the exception of cholestyramine and cholestypol as long as medical regimen has been stable for at least 6 weeks prior to randomization
• No clinically significant laboratory abnormalities
• Negative urine drug screen
• Negative serum pregnancy test in women of child-bearing potential
• Women of child-bearing potential must be non-lactating, and agree to use acceptable contraception throughout the study period and for 30 days after discontinuation of study drug
• Able to comply with all required study procedures and schedule
• Able to speak and read English
• Willing and able to give written informed consent

Exclusion Criteria:

• Obesity of known endocrine or genetic origin (e.g., untreated hypothyroidism, Cushing's syndrome, polycystic ovary syndrome)
• Serious medical condition
• History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer.
• History of suicide attempt or serious psychiatric illness
• History of Major Depressive Disorder within the past 2 years
• In need of medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months prior to randomization
• Type I or Type II diabetes
• History of alcohol or drug abuse or dependence as determined by the Investigator within 1 year prior to randomization
• History of surgical or device (e.g. gastric banding) intervention for obesity
• History of seizures or predisposition to seizures
• History of hypersensitivity to sulfonamides ("sulfa"), bupropion, or zonisamide
• History of treatment with bupropion SR (Wellbutrin, Zyban) or zonisamide (Zonegran) within previous 12 months
• History of nephrolithiasis (renal calculi)
• Loss or gain of more than 4.0 kg within 3 months prior to randomization
• Women of child bearing potential not adhering to a medically acceptable form of contraception
• Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug