Adverse lifestyle factors increase risk of anxiety and depression in young adults. Consequently, neurochemical and neuroanatomical alterations ensue, and may initiate a vicious cycle of mental distress, poor lifestyle choices and academic performance. A total of 558 students from different US colleges completed an anonymous survey on academic performance, daytime sleepiness, substance use and mental distress. Low mental distress in college students positively associated with good academic efforts and limited daytime sleepiness. Mild mental distress correlated with borderline work neglect and with a marginal negative association with Grade-point average (GPA). Severe mental distress correlated with excessive daytime sleepiness and poor academic performance. A System Dynamic model was developed to reflect the integration of these variables with mental distress and academic performance. Our results demonstrate that manageable lifestyle factors contribute to mental health in college students, which become potentially cyclic events that may impact academic performance.