Background: Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive). Methods: The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated. Results: Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type.