Over the past four decades, advances in medicine have decreased the mortality rates of many previously fatal chronic diseases. Children who would have died early in life are now living well into adulthood, and many are matriculating as college students. Data regarding the prevalence of chronic illness among college students, the college experience of chronically ill students, and why such students are at greater risk of failing to graduate from college are limited. More and more youth with chronic illness are entering college each year, yet there is a major gap in the understanding of how the experience of being a first-year student differs for chronically ill students and healthy students. This study was designed to examine the experience of being chronically ill and transitioning to college by addressing the following research questions: (a) Do chronically ill college first-years and their healthy peers differ in health-related quality of life and measures of loneliness? and (b) Do college first-years use available health services and other resources? An invitation to participate in an online survey was e-mailed to the first-year class at a private university within 1 month of enrolling. Approximately 10% of the freshmen class (163 students) completed the survey. This study found that students with either physical or mental chronic illness had lower Health Related Quality of Life scale (HRQoL) and higher loneliness scores as compared to their healthy peers. Yet few first-year students with a chronic illness used the resources available at the college. Colleges should be aware of the increased challenges faced by chronically ill first-year students, including issues surrounding medical transition, higher rates of loneliness, and lower HRQoL.