Background: Students at universities frequently encounter a variety of stressors, making them more susceptible to psychological issues that might harm their mental, emotional, and physical well-being. Objectives: To assess the prevalence and predictors of depressive symptoms among Menoufia University students in Shebin Alkom City, Menoufia Governorate. Patients and methods: This study was a cross-sectional study conducted on 400 students. They were interviewed using a predesigned interview questionnaire, which was distributed to the participants in Shebin Alkom faculties. Results: There were significant differences between the studied group with depressive symptoms regarding social and academic predictors for depressive symptoms as family problems, habits, physical activities, study factors, financial pressures, and romantic relationships. There were significant differences between the studied group with depressive symptoms regarding medical problem, physical factors, and family history of mental illness as predictors for depressive symptoms among the studied students. Normal body mass index was the most frequent among non-depressed group and depressed patients. The results of binary logistic regression analysis indicated that crowding index, socioeconomic data, physical activities, family history of mental illness, study factors, obesity, financial pressures, and romantic relationships were the most significant predictors with Odds ratio of 2.9, 21.61, 3.13, 5.3, 4.34, 3,18, 3.48 and 0.413 respectively (p < 0.05). Conclusion: It is concerning that a high percentage of university students have depressed symptoms, it was found in 41.5% among university students under study. It was more prevalent among students with crowding index ≥2,low or moderate socio-demographic score, low physical activity, theoretical study, financial pressures, family history of mental illness, overweight, and romantic relationships.