The purpose of this study is to test serial-multiple mediation role of self-esteem and perceived social support on the relationship between university students' loneliness and life satisfaction. The participants of this study consisted of 398 undergraduate students, with 289 females and 109 males aged between 17 and 41 with a mean age of 21.79 (SD = 3.23). This study examined the statistical significance of the mediation effects in the tested model through the Ordinary Least Squares Regression Model and the Bootstrap method. The results showed that mediation effect of self-esteem and perceived social support variables solely were found be higher on the relationship between loneliness and life satisfaction than when both of them were entered into the model together. Single mediation effect of each variable did not differ. Focusing on students' perceived social support and self-esteem may be useful to increase students' life satisfaction in universities. This study may also be a resource for college counselors and mental health professionals to create protective and preventive approaches when working with students.