background Depression negatively affects cognitive functioning and, consequently, academic performance. Studies of this association have yielded conflicting results and have not fully considered other factors that may play a role in academic performance. This study examines the relation between depression and academic performance in students at a large urban university in North Carolina. methods We analyzed data from student responses to the 2008 cross-sectional National College Health Assessment to create categories of depressive symptomatology. E-mail invitations to participate in the assessment were sent to 8,000 students at the university in an effort to obtain at least 900 responses, the minimum number considered valid for a campus of its size. We analyzed the responses of the 1,280 undergraduates who completed the survey. Logistic regression analyses were performed to examine associations between depressive symptoms and academic performance in this group. results Students in the second, third, and fourth quartiles of depressive symptomatology had increased, though statistically non-significant, odds of having a lower cumulative grade average, even after adjustment for age, sex, year in school, race/ethnicity, substance use, and level of credit-card debt. This difference was most pronounced among students in the second quartile of depressive symptomatology. limitations This cross-sectional study did not allow for evaluation of causality. In addition, the self-report nature of this questionnaire could have led to some inaccuracy in reporting. conclusions Students reporting even a small number of depressive symptoms may be at increased risk for academic problems.