Poor mental health is associated with physical illness, but this association is poorly characterized among college students. Objective and Participants: Using American College Health Association-National College Health Assessment data, the authors characterized poor mental health (depression, anxiety, negative affect) and examined the relationship between poor mental health and acute infectious illnesses (bronchitis, ear infection, sinusitis, strep throat) among 47,202 US college students. Methods: The authors used frequency and cross-tabulation analyses to characterize mental health and determine univariate associations among variables. They used binary logistic regression to determine the association between poor mental health and acute infectious illness, controlling for research-derived covariates. Results: The prevalence of acute infectious illness ranged from 8% to 29%. The prevalence of anxiety and depression ranged from 12% to 20%, respectively. Depression, anxiety, and exhaustion were associated with acute infectious illness across all dependent measures, with odds ratios ranging from .56 to .91. Conclusions: Poor mental health is associated with acute infectious illness among college students.