Background: Sleep is an essential need which if distressed, causes negative insults on quality of life. Poor sleep quality affects academic performance, epically if the academic load is large and required full attention and activity. Objectives: This study aimed to assess factors affecting sleep quality of medical students in Menoufia University. Methods:  Self-administered, Pittsburgh Sleep Quality Index (PSQI) questionnaire was used. The study sample was involving 505 randomly selected medical students from first to six year. Results: Prevalence of poor sleep quality was at more than half (58.5%) of medical students. Poor sleep quality was detected more in the first three years students. Statistical significant effect of female sex, BMI, and sharing room with others was reported. Significant factors related to poor sleep quality was presence of learning difficulties, worry about exams and the need of sleep late and getting up early. Poor sleep quality was significantly affecting participation in routine and social activities, depressed mood, attention deficit, being late for morning classes and loss of enthusiasm in doing ordinary subjects. Conclusion: Sleep Quality among medical students affected by factors which if handled may improve their academic performance. Poor sleep quality affects daily activity, attention and keeping enough enthusiasm of medical students to perform their required tasks.