This study quantified optimism, emotional intelligence, and depression levels, and explored potential key factors affecting the depression level in undergraduate students. We performed a survey targeting undergraduate students in two Universities at D city and S city, between April 8th and 30th of 2016. After receiving informed consent, a total of 166 university students were recruited. They were asked to fill in a self-reported questionnaire about optimism, emotional-intelligence, and depression. The data were analyzed through descriptive statistics, Pearson's correlation coefficient, and multiple regression analysis using IBM SPSS version 22.0. The data analysis results showed that the mean score for optimism was 3.67±0.51, 3.66±0.49, and 3.69±0.55 for overall undergraduate students, undergraduate nursing students, and undergraduate non-nursing students, respectively. Moreover, the mean score of emotional intelligence was 3.56±0.49, 3.53±0.49, and 3.60±0.51, respectively. In addition, the mean score of depression was 8.28±7.48, 10.97±7.65, and 5.50±5.54, respectively. It was revealed that a strong negative correlation exists among optimism, emotional intelligence, and depression. This correlation was stronger for undergraduate nursing students than undergraduate non-nursing students. Optimism and emotional intelligence were key factors influencing depression. The degree of this influence was higher for undergraduate nursing students than undergraduate non-nursing students. In conclusion, a program that empowers optimism and emotional intelligence is necessary to manage depression for undergraduate students.