Background: Epilepsy, one of the most common serious chronic brain disorders, is poorly understood by the public and has been associated with numerous misconceptions and beliefs. This, coupled with its sometimes dramatic clinical manifestations, has often resulted in a strong social stigma.

Objective: This study was conducted to find out knowledge, attitudes and practices toward epilepsy among preparatory school students in Mekelle, North Ethiopia.

Methods: A semi-structured questionnaire used previously by various authors was self-administered to 391 students studying in four preparatory schools in Mekelle, North Ethiopia.

Results: About 85.7% had heard about epilepsy, 19.23% had read on the subject, 67.03% had known someone with epilepsy and 57.14% had witnessed a seizure. Those who would offer equal employment opportunities to people with epilepsy (PWE), refuse to associate with, or refuse to marry PWE represented 64%, 16.8%, and 44.8%, respectively. Negative attitudes seemed to be reinforced by beliefs that epilepsy is evil spirit (33.24%), contagious (28.6%) or a kind of insanity (51.6%). Majority of respondents (70.33%) opted for Holy water, followed by physicians (64.01%), traditional healer (44.78%) and prayers (32.14%).

Conclusions: The study revealed practices and knowledge toward epilepsy were limited, especially with respect to epilepsy’s cause, manifestation, and management. Moreover, there were statistically significant differences between respondents attitude with respect to epilepsy based on age, gender, level of education, religion and school category