Objective: To compare the extent to which information efficacy (confidence for acquiring useful information) and media literacy skills predict knowledge and self-efficacy for preventing or treating the health threat of influenza. Participants: A random-sample survey of 1,379 residential students enrolled at a northwestern public university was conducted in fall 2009. Methods: Students accessed an Internet survey through a link provided in an e-mail. Results: Students who self-diagnosed correctly demonstrated higher levels of media literacy skills than those who self-diagnosed incorrectly. Among those who self-diagnosed incorrectly, the only predictor of knowledge was accessibility of information sources; low accessibility was associated with reduced knowledge. Information efficacy predicted self-efficacy for both groups. Conclusions: The results illustrate the limitations of information efficacy in the absence of media literacy skills. To decrease health risks, college health practitioners should promote media literacy while also ensuring easy access to high-quality information. (Contains 3 tables.)