Aims & Objectives: To determine and compared the effect of Valproate and levetiracetam monotherapy on Thyroid and lipid profile in children with seizure disorder. Material and Methods: This comparative study will be carried out in Department of Paediatrics. The study population will be children with seizure disorder aged 1-15 years patient who registered and in follow up in O.P.D of guru Gobind Singh Medical hospital receiving levetiracetam or valproate monotherapy for more than 6 months. Thirty children will be enrolled in each group (Valproate and levetiracetam). After obtaining the written and informed consent from the parent/guardian of the children baseline details will be recorded as per a predesigned proforma. Fasting serum sample of 1.5 ml each for thyroid function (T3, T4 and TSH) and lipid profile (Total Cholesterol, Triglycerides, HDL-C LDL-C) will be obtained between 8.00and 10.00 a.m. in plain vial. Samples will be transported to lab immediately with icepack and processed immediately. Thyroid function will be processed by chemiluminescent immunoassay method by Beckman Coulter analyser. Lipids profile will be processed by Beckman Coulter Analysers. Reference range for Thyroid functions and lipid profile will be taken as per our laboratory references. Results: In the VPA group, male patients comprised 37.5%, which was lower compared to 50% in the Levetiracetam group. This difference was not statistically significant (p = 0.321). The sex ratio in the VPA group was 0.6:1 for males to females, indicating a higher proportion of females in the Valproate group. The mean weight, height, and mid-upper arm circumference in the Valproate group were 30.6 ± 15.66 kg, 122.03 ± 28.39 cm, and 11.17 ± 1.26 cm, respectively, compared to 24.13 ± 11.91 kg, 114.1 ± 25.41 cm, and 11.34 ± 1.4 cm in the Levetiracetam group. Although there was a trend toward higher weight, greater height, and higher body mass index in the Valproate group, these differences were not statistically significant (p > 0.05). MRI scans were performed in 24 patients—14 from the Valproate group and 10 from the Levetiracetam group. The remaining 38 patients were clinically diagnosed with epilepsy and managed with antiepileptic drug (AED) therapy without MRI imaging. In the Valproate group, MRI findings were normal in 2 patients (6.25%), whereas in the Levetiracetam group, MRI was normal in 5 patients (16.67%). Specific abnormalities in the Valproate group included one case each of encephalitis and West syndrome, hyperintensities with meningeal enhancement, and neurocysticercosis. Additionally, two patients had hyperintensity in the periventricular region, and two had periventricular leukomalacia. In the Levetiracetam group, hemicortical atrophy and non-communicating hydrocephalus were observed in one patient each. MRI findings suggestive of sequelae of hypoxic insult or hypoxic-ischemic encephalopathy (HIE) were seen in 5 patients (15.8%) in the Valproate group and in 3 patients (9.99%) in the Levetiracetam group. However, these differences in MRI findings between the two groups were not statistically significant (p > 0.05). Electroencephalography (EEG) was conducted in only 7 patients—3 in the Valproate group and 4 in the Levetiracetam group. EEG was not performed in the remaining 55 patients (90.63% in the Valproate group and 86.67% in the Levetiracetam group), who were clinically diagnosed with seizures. Among the patients who underwent EEG, one patient in the Valproate group showed seizure activity, and another showed wave slowing. In the Levetiracetam group, two patients had seizure activity, and one had generalized wave slowing. The EEG findings between the two groups were also not statistically significant (p > 0.05). Conclusion: The present study is one of the first studies from North India in a Government Medical College to exclusively assess the effect of valproic acid (VPA) and levetiracetam (LEV) therapy on thyroid and lipid profile in children presenting with seizures. The role of VPA on disturbance in thyroid hormone milieu can be observed in our study in the form of mean elevation of TSH levels significantly in VPA vs LEV group. At the same time, we can see the protective role of LEV therapy on lipid profile parameters in having a statistically significant reduction in the various ratios, viz LDL/HDL, TGs/HDL and TC/HDL ratio. This finding can be of paramount importance in deciding the ideal treatment of children with seizure disorders in future, especially with underlying atherogenic potential. But, further prospective studies with an increased sample size considering the various confounders and involving a healthy control group can give definitive guidance in this regard in the future.